KL-6 is a high-molecular-weight glycoprotein classified as a human MUC1 mucin. It was hypothesized that KL-6 could be detectable in the circulating blood and especially in airway secretions in lung diseases associated with mucus production such as chronic obstructive pulmonary disease (COPD). Additional aims of this study were to investigate whether the levels of KL-6 in plasma and sputum are related to ageing and smoking history.
The concentrations of KL-6 in plasma and induced sputum supernatants from young and/or middle aged/elderly non-smokers, smokers and patients with COPD were assayed by ELISA (n = 201). The subjects were classified into five groups according to age, smoking status and presence of COPD. In addition, KL-6 expression in control and diseased lung i.e. samples from patients with COPD (n = 28), were analyzed by immunohistochemistry and digital image analysis.
The plasma levels of KL-6 increased with age both in non-smokers and smokers. Among middle aged/elderly subjects, plasma KL-6 levels in all smokers regardless of COPD were significantly higher than in non-smokers, whereas sputum levels of KL-6 were significantly higher in COPD compared not only to non-smokers but also to smokers. KL-6 was more prominently expressed in the bronchiolar/alveolar epithelium in COPD than in the control lungs. Plasma and sputum KL-6 levels correlated inversely with obstruction and positively with smoking history and ageing. The linear multiple regression analysis confirmed that age and cigarette smoking had independent effects on plasma KL-6.
KL-6 increases with ageing and chronic smoking history, but prospective studies will be needed to elucidate the significance of KL-6 in chronic airway diseases.
Cites: Curr Drug Targets Inflamm Allergy. 2005 Aug;4(4):465-7016101523
Cites: Am J Respir Crit Care Med. 1997 Jul;156(1):109-159230733
Cites: Am J Respir Crit Care Med. 2006 Jul 1;174(1):6-1416556692
Cites: Respir Res. 2006;7:6916646959
Cites: Eur Respir J. 2006 Sep;28(3):523-3216611654
Cites: Eur Respir J. 2007 Jan;29(1):51-517050565
Cites: Am J Respir Crit Care Med. 2007 Sep 15;176(6):532-5517507545
Lung tissues from workers at the Mayak Production Association were examined to determine the distribution of plutonium (Pu) activity in various lung compartments. Stereological sampling methods and autoradiography were used. Pu particles were identified by microscopic examination of autoradiographs and localised in one of six normal anatomic sites and two sites of fibrosis (parenchymal, non-parenchymal). Particle activity was determined by counting the number of tracks emanating from the particles. Over 50% of the Pu activity was localised in sites of fibrosis, which had significantly higher than average activity for the lung. Over 40% of the activity was in lung parenchyma. Activity in the bronchovascular interstitium was significantly lower than average. These results support the hypothesis that Pu activity is not uniformly distributed in the lung, with long-term retained particles concentrated in scars of the lung. The results may significantly affect estimates of dose from inhaled Pu.
A single intraperitoneal injection of GdCl(3)in doses of 14 or 28 mg/kg to mice with intravenously transplanted Lewis pulmonary adenocarcinoma on days 3 or 8 after tumor transplantation reduced the mean number of tumor metastases in the lungs. The effect of GdCl(3)was more pronounced if it was injected at the stage of tumor dissemination (day 8). The positive antimetastatic effect of GdCl(3)was presumably due to its capacity to macrophage depression. The direct (not mediated through mononuclear phagocyte system cells) effect of GdCl(3)on tumor cells cannot also be excluded.
Inhibition of antigen-induced eosinophilia and airway hyperresponsiveness by antisense oligonucleotides directed against the common beta chain of IL-3, IL-5, GM-CSF receptors in a rat model of allergic asthma.
Airway obstruction, hyperresponsiveness, and the accumulation and persistence within the airways of inflammatory cells characterize asthma. Interleukin (IL)-3, granulocyte macrophage colony- stimulating factor (GM-CSF), and IL-5 are among several cytokines that have been shown to be increased in asthma and to contribute to atopic inflammation. They mediate their effect via receptors that have a common beta subunit (beta(c)). We hypothesized that blocking of this common beta(c) would impair the airway response to antigen. We report that an antisense (AS) phosphorothioate oligodeoxynucleotide (ODN) found to specifically inhibit transcription of the beta(c) in rat bone marrow cells also caused inhibition of beta(c) mRNA expression and of immunoreactive cells within the lungs of Brown Norway (BN) rats when injected intratracheally (p
Results obtained in a study of the microscopic distribution of plutonium in the lungs of deceased Pu workers from the Mayak Production Association showed that the long-term retention of Pu was greater than predicted by the current ICRP 66 respiratory tract dosimetry model (HRTM). These data were therefore applied to the HRTM by modifying selected parameters, namely the transfer rate of Pu from the transformed state compartment and the fraction of Pu that transfers to the bound state compartment. Invoking the latter compartment into the modelling allowed a better representation of the long-term Pu retention as well as providing a convenient means of describing the workplace-specific characteristics of the different Pu aerosols found in the Mayak plant. In particular, the present model describes a significantly greater long-term retention of Pu nitrate aerosols in the lung compared with the Type M default.
to assess mutational events in exons 5, 7, and 8 of the p53 gene and to reveal mutant p53 protein in verified cases of morphologically altered (proliferative and precancerous changes, lung cancer) and histologically unaltered, lung tissues in workers exposed to occupational radiation.
The investigation used formalin-fixed paraffin-embedded unaltered and altered lung tissue blocks (FFPBs) obtained from the human radiobiological tissue repository. The shelf-life of FFPBs was 5-31 years. An immunohistochemical technique using mouse antibodies against p53 protein (, Denmark), stained with diaminobenzidine (DAB) chromogen, was employed to determine p53 protein. DNA was isolated from lung tissue FFPBs with QIAmp DNA FFPE Tissue Kit, (, USA). Polymerase chain reaction (PCR) was performed to amplify the p53 gene exons 5, 7, and 8 selected for examination, by applying the sequences of genes and primers, the specificity of which was checked using the online resource (http://www.ncbi.nlm.nih.gov/blast). PCR products were detected by temporal temperature gradient gel-electrophoresis and the Sanger sequencing method. The obtained DNA fragments were analyzed on a sequencer ABI Prism 3100 Genetic Analizer (, USA). Computer-aided DNA analysis was made using the BLAST program. A package of applied Statistica 6.0 programs was employed for statistical data processing. Results. Immunohistochemical analysis showed that mutant p53 protein was absent in the cells of unaltered lung tissue and the number of cells with mutant p53 protein increased in all the patients with proliferative and precancerous changes and lung cancer, suggesting p53 protein dysfunction. The total number of p53 gene mutations in exons 5, 7, and 8, if there were proliferative and precancerous lung tissue changes and lung cancer, were 25, 20, and 40%, respectively. All the found mutations were transversions (the substitution of purine for pyrimidine or, conversely), indicating the action of exogenous mutagens.
The results of this investigation have confirmed other investigators' data showing that p53 gene mutations in lung cancer are observed in 40-70% of cases. The differences in the number of cases of altered lung tissue with mutations in the p53 gene (not more than 40%) and in those of p53 protein expression were found in 100%, suggesting the regulation of p53 gene function in the cell at multiple levels.
An analysis of modern methods of diagnostics such as morphological, immunohistochemical and spectral, which included the bronchoscopy and spectrometry by using reflectance and autofluorescent regime, was made. The data involved the results of prospective follow-up study of 167 patients (620 biopsies). An obligatory spectrometry of suspicious area was carried out before the forceps biopsy. The microslides, which met the requirements of criteria of one of the carcinogen steps (n=201), were subjected to the in-depth morphological and immunohistochemical investigations. The tendency of angiogenesis (CD31 and CD34), proliferative activity (Ki-67), level of apoptosis (P53), EGFR expression were estimated. The sensitivity of combined endoscopic method was 94,74% by specificity 79,95% and high prognostic value of negative endoscopic diagnosis - 99,4%.
The degree of nonuniform distribution of plutonium in the human lung has not been determined; thus current dosimetric models do not account for nonuniform irradiation. A better scientific basis is needed for assessing the risk of developing radiation-induced disease from inhaled alpha-particle-emitting radionuclides. We measured the distribution of plutonium activity in the lung by autoradiography and related the activity to specific compartments of the lung. The study materials were lung specimens from deceased workers employed by the Mayak Production Association. The approach to analyzing these lung samples used contemporary stereological sampling and analysis techniques together with quantitative alpha-particle autoradiography. For the first time, plutonium distribution has been quantified in the human lung. The distribution of long-term retained plutonium is nonuniform, and a significant portion of plutonium was retained in pulmonary scars. In addition, a large fraction of plutonium was present in the parenchyma, where it was retained much longer than was estimated previously. The sequestration of plutonium particles in scars would greatly reduce the radiation exposure of the critical target cells and tissues for lung cancer. Thus the prolonged retention of plutonium in lung scars may not increase the dose or risk for lung cancer.
AIM: To estimate the selectivity of action of cobalt complexes on tumor tissue. MATERIALS AND METHODS: Cobalt(III) complexes containing both the tetradentate Schiff-base ligand derived from acetylacetone and ethylenediamine, and compounds of the vitamin PP series or their synthetic analogs, viz. nicotinamide, isonicotinamide or nicotinic acid, as extra (axial) ligands, were tested in vivo on transplanted mice tumors, namely Lewis lung carcinoma (3LL), melanoma B16, and mammary adenocarcinoma Ca755. concentrations of malondialdehyde in tissue extracts were measured by standard biochemical methods. The rate of DNA unwinding was used to detect DNA damage in tumor cells. Level of tumor hypoxia as well as bioenergetic status were estimated using 31P NMR spectroscopy in perchloric acid extracts of tissue. RESULTS: A significant and selective increase of malondialdehyde in tumor tissue reflecting activation of lipid peroxidation was found after administration of the complexes. The bioenergetic status in tumor was also selectively affected by the complexes: minimization of signals of high-energy phosphates was observed two hours after injection of the complexes. An increase of the number of DNA single-strand breaks was registered in tumor tissue, supporting the suggestion that the complexes may directly affect DNA. A correlation between the above tumor effects and the structure of axial ligands was demonstrated. CONCLUSION: Cobalt(III) complexes affect tumor tissue with a very high level of selectivity; in particular they activate lipid peroxidation, induce DNA single-strand breaks, suppress the bioenergetic status, and enhance hypoxia. It is supposed that the selective action of these complexes on tumor tissue is due to peculiarities of tumor microphysiology, in particular significant tumor hypoxia.