CFTR (cystic fibrosis transmembrane conductance regulator), MDR1 (multidrug resistance), and MRP1 (multidrug resistance-associated protein), members of the ABC transporter superfamily, possess ...multiple functions, particularly Cl–, anion, and glutathione conjugate transport and cell detoxification. They are also hypothesized to have a number of complementary functions. It is generally accepted that data obtained from nasal mucosa can be extrapolated to lower airway cell physiology. The aim of the present study was to investigate by immunohistochemistry the differential localization of CFTR, MDR1, and MRP1 in the normal mucosa of 10 human nasal turbinates. In ciliated epithelial cells, CFTR was inconstantly expressed at the apical cell surface, intense membranous labeling was observed for MDR1, and intense cytoplasmic labeling was observed for MRP1. In the glands, a higher level of expression was observed on serous cells, at the apical surface (for CFTR), on lateral membranes (for MDR1), and with an intracytoplasmic distribution (for MRP1). In conclusion, CFTR, MDR1 and MRP1 are expressed in the epithelium and glands of the nasal respiratory mucosa, but with different patterns of expression. These results suggest major roles for CFTR, MDR1, and MRP1 in serous glandular cells and a protective function for MDR1 and MRP1 in respiratory ciliated cells.
To assess the significance of S-phase fraction (SPF) and DNA ploidy evaluated by DNA flow cytometry as prognostic markers in stage I or II breast cancer.
A series of 271 patients, treated by surgery, ...radiotherapy +/- systemic therapy was analyzed (median follow up: 64 months). Standardized flow cytometry cell preparation from frozen samples and consensus rules for data interpretation were followed. Three SPF classes were defined on the basis of tertiles after adjustment for ploidy. Four groups were defined based on combinations of DNA ploidy (DIP: diploid; ANEUP: aneuploid) and SPF: DIP and low SPF (DL, n=37), DIP and medium or high SPF (DMH, n=76), ANEUP and low SPF (AL, n=24), ANEUP and medium or high SPF (AMH, n=68). Local control rate (LCR), disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS) were correlated with DNA ploidy, SPF, DL to AMH groups, T and N stages, SBR grading, age, and hormonal status on univariate and multivariate analysis (Cox model).
On univariate analysis, DFS and LCR were higher for DIP tumours. High SPF values were associated with shorter DFS. LCR, MFS, DFS, and OS rates were significantly different with an increasingly poorer prognosis from DL to AMH. On multivariate analysis, groups DL to AMH, histological node involvement and T stage were independently associated with MFS, and DFS. In N- patients, DL to AMH remained independent for MFS and DFS. For SBR III tumours, MFS and OS were significantly different in DL to AMH groups. These results strongly support the use of combined evaluation of DNA ploidy and SPF as independent parameters in clinical trials for N- stage I and II breast cancer.
: Malignant pleural mesothelioma (MPM) results from neoplastic transformation of mesothelial cells. Past asbestos exposure represents the major risk factor for MPM, as the link between asbestos ...fibres and MPM has been largely proved by epidemiological and experimental studies. Asbestos fibres induce DNA and chromosome damage linked to oxidative stress following phagocytosis. Recently, simian virus 40 (SV40) has been implicated in the aetiology of MPM. The origin of human infection has been associated with SV40‐contaminated polio vaccines, although to date, no epidemiological data supports this hypothesis. SV40 may act as a coactivator of asbestos in mesothelial oncogenesis. The transforming potency of SV40 results from the activity of two viral proteins, large T and small t antigens. SV40 infection stimulates production of growth factors elsewhere implicated in autocrine growth of mesothelioma cells and inactivates RASSF1, a gene silenced in MPM. Roles for ionising radiation, chemicals or genetic factors have also been suggested from the observation of sporadic MPM cases or animal studies. Genetic alterations in the tumour suppressor genes, P16/CDKN2A and neurofibromatosis 2 (NF2), are found both in human MPM and in asbestos‐exposed Nƒ2‐deficient mice. MPM is still of great international concern. Despite a ban on asbestos use in Western countries, the incidence of MPM is increasing, due to the long delay between asbestos exposure and diagnosis. Moreover, asbestos is still used in developing countries. The implication of other risk factors, especially SV40, supports a need for further research into MPM.
The prevalence of pulmonary toxoplasmosis was assessed by a prospective analysis of 144 bronchoalveolar lavage (BAL) samples using competitive polymerase chain reaction (PCR) to avoid false-negative ...results due to PCR techniques. Six samples were excluded because they contained amplification reaction inhibitors. None of the samples from the 37 immunocompetent patients and only 1 sample (1.7%) from the 59 immunocompromised patients without human immunodeficiency virus infection were PCR-positive. In contrast, Toxoplasma gondii DNA was found in 6 (14%) of 42 samples from patients with AIDS. All 6 patients had ⩾40 CD4 cells/µL and anti-Toxoplasma antibodies, and 5 had other sites of Toxoplasma infection. Six other AIDS patients who had received treatment for cerebral toxoplasmosis were PCR-negative. Thus, pulmonary toxoplasmosis is frequent in AIDS patients who have other sites of Toxoplasma infection and low CD4 lymphocyte counts and who are not receiving prophylaxis.
To establish the diagnosis of alveolar hemorrhage (AH) in cells recovered by bronchoalveolar lavage (BAL), Golde and colleagues created a score based on the hemosiderin content of alveolar ...macrophages stained with Prussian blue. We used an easier method, calculating the percentage of siderophages among the total alveolar macrophages recovered by BAL. We have retrospectively studied this method in 240 BALs performed in 194 immunocompromised patients. Prussian blue staining was performed on each BAL sample, and the Golde score was calculated for 47 samples chosen at random. The methods were compared for diagnosing AH. The percentage of siderophages correlated well with the Golde score. AH was defined by at least 20% siderophages. This definition was validated by comparison with the method of Kahn and coworkers. AH was present in 87 (36%) of the samples and was significantly associated with four parameters: thrombocytopenia (< 50,000/mm3), other abnormal coagulation parameters, renal failure (creatinine > or = 2.5 mg/dl), and a history of heavy smoking. The diagnosis of AH did not correlate with either the cause or the outcome of pneumonia. AH was seen more frequently in cardiac transplant patients (75%). In our experience, (1) a percentage of siderophages > or = 20% is sufficient and is an easier determinant of the diagnosis of AH than the Golde score; and (2) AH is rarely the sole cause of lung injury and is usually associated with other causes of pneumonia. AH may be considered more as a sign than as a distinct disease in this population.
Biallelic NF2 gene inactivation is frequently found in human malignant mesothelioma. In order to assess whether NF2 hemizygosity may enhance susceptibility to asbestos fibres, we investigated the Nf2 ...status in mesothelioma developed in mice presenting a heterozygous mutation of the Nf2 gene (Nf2(KO3/+)), after intraperitoneal inoculation of crocidolite fibres. Asbestos-exposed Nf2(KO3/+) mice developed tumoural ascites and mesothelioma at a higher frequency than their wild-type (WT) counterparts (P&<0.05). Six out of seven mesothelioma cell lines established from neoplastic ascitic fluids of Nf2(KO3/+) mice exhibited loss of the WT Nf2 allele and no neurofibromatosis type 2 protein expression was found in these cells. The results show the importance of the NF2 gene in mesothelial oncogenesis, the potential association of asbestos exposure and tumour suppressor gene inactivation, and suggest that NF2 gene mutation may be a susceptibility factor to asbestos.
Recombinant human interferon gamma (r-hu-IFNgamma) exerts both antitumoral activity in the early stages of human malignant mesothelioma and a cytostatic effect in human mesothelioma (HM) cell lines ...in vitro. The antiproliferative effect of interferons (IFNs) reported in a variety of cells has been attributed to several mechanisms. In order to progress in the understanding of HM cell growth modulation by r-hu-IFNgamma, modifications of cell cycle progression and expression of key cell cycle regulator proteins in response to r-hu-IFNgamma were examined. Nine HM cell lines were studied, including one resistant to the antiproliferative effect of r-hu-IFNgamma. Except in the resistant cell line r-hu-IFNgamma produced an arrest in the G1 and G2-M phases of the cell cycle, associated with a reduction in both cyclin A and cyclin dependent kinase inhibitors (CDKIs) expression. Moreover cyclin B1/cdc2 activity was decreased. The present study provides the first evidence of a G2-arrest in r-hu-IFNgamma-treated HM cell lines and indicates that HM cell lines, despite their tumorigenic origin still support cell cycle control. The cell cycle arrest induced by r-hu-IFNgamma seems to depend on cyclin regulation through p21(WAF1/CIP1)- and p27(Kip1)-independent mechanisms and is not directly related to the induced DNA damage.
L’espace pleural, dérivé du cœlome intra-embryonnaire, est limité par une séreuse dont le mésothélium possède non seulement des caractéristiques de cellules épithéliales de revêtement mais également ...des potentialités de cellules sécrétrices, en particulier de cytokines et de facteurs de croissance. Les plèvres viscérales ont une vascularisation sanguine différente selon les espèces ; quant à la circulation lymphatique, elle a la particularité d’être directement connectée avec l’espace pleural par des pores au niveau de la plèvre pariétale. La physiologie pleurale et les mouvements du liquide pleural sont donc directement liés aux structures particulières de la plèvre.
The pleural space, derived from the intraembryonic coelom, is limited by a serous membrane including the mesothelium formed by cells possessing not only the characteristic features of epithelial cells but also the potential of secretory cells (cytokines and growth factor). Blood supply to visceral pleurae differs depending on the species while the lymphatic circulation is directly connected to the pleural space via pores in the parietal pleura. Pleural physiology and movement of pleural fluid are directly related to the particular structures of the pleura.
The diagnostic procedure of chronic pulmonary opacities may envisage the search for non-Hodgkin lymphoma (NHL). Previous retrospective studies have shown that clonality analysis of bronchoalveolar B ...lymphocytes could reflect the clonality of pulmonary lymphocytes. Our objective was to define the diagnostic usefulness of bronchoalveolar lavage (BAL) B-lymphocyte clonality analysis in the setting of a clinical suspicion of both primary and secondary pulmonary lymphoma. A prospective BAL fluid B-cell clonality analysis was performed by polymerase chain reaction (PCR) in 106 consecutive patients presenting with a clinical suspicion of pulmonary NHL. Diagnosis was pulmonary B-cell lymphoma for 22 patients (13 primary and 9 secondary). When compared, pulmonary biopsy and BAL fluid have clonal identity. The detection of a strong B-cell clonal population in BAL fluid was associated with the diagnosis of pulmonary NHL (P< .0001), with a 97% specificity and a 95% negative predictive value. Thus, the absence of a dominant B-cell clone detection in BAL fluid could help to dismiss invasive investigations of pulmonary lesions. The detection of a dominant B-cell clone would lead to the performance of a pulmonary biopsy to get histologic diagnosis in primary pulmonary lymphoma and, by contrast, would avoid the need for biopsy in the setting of a secondary pulmonary lymphoma. (Blood. 2004;103: 3208-3215)
PDF
