Activation of human epithelial lung a549 cells by the pollutant sodium sulfite: enhancement of neutrophil adhesion.

Air pollutant exposure may induce deterioration of respiratory health. Concentrations of air particles, ozone, nitrogen dioxide, sulfur dioxide, and sulfate are among the players involved in the initiation and/or exacerbation of lung diseases. We have previously documented that the pollutant sodium sulfite (Na(2)SO(3)) is a human neutrophil agonist. To date, there is no evidence in the literature that Na(2)SO(3) can activate epithelial lung cells. In the present study, we found that Na(2)SO(3) (0.01-10 mM) induces tyrosine phosphorylation events and interleukin-8 production in human epithelial lung A549 cells. In addition, we found that Na(2)SO(3) did not promote A549 cell apoptosis as assessed by the degradation of the cytoskeletal gelsolin protein and by FITC-annexin-V binding. Human neutrophil adhesion to Na(2)SO(3)-induced A549 cells was increased when compared with untreated A549 cells. As assessed by flow cytometry, cell surface expression of intercellular adhesion molecule (ICAM)-1, ICAM-3, and vascular cell adhesion molecule-1 (VCAM-1) on A549 cells was not affected by Na(2)SO(3). We conclude that Na(2)SO(3) can activate A549 cells. In addition, we conclude that neutrophil adhesion to Na(2)SO(3)-induced A549 cells is increased via an ICAM-1-, ICAM-3-, and VCAM-1-independent mechanism.     

Effects of interleukin-2 on gene expression in human neutrophils

Recently, the interleukin-2 receptor (IL-2R) was shown to be present on human neutrophils, and IL-2-neutrophil interactions are believed to be important in both tumor rejection and increased susceptibility to bacterial infections. Furthermore, neutrophils have been shown to synthesize host defense proteins, such as cytokines. In this study, we analyzed the effects of IL-2 on the induction of de novo RNA and protein synthesis in this cell type. When cells were stimulated with IL- 2 alone, the level of incorporation of either [5-3H]-uridine or [35S]- methionine and [35S]-cysteine was similar to unstimulated cells. However, when cells were stimulated with the combination of a fixed concentration of granulocyte-macrophage colony-stimulating factor (GM- CSF), a dose-dependent effect of IL-2 was observed on the induction of both RNA and protein synthesis. In the presence of tumor necrosis factor-alpha or formyl-methionyl-leucyl-phenylalanine, however, IL-2 exerted no similar effect. Furthermore, the study of a large number of normal subjects (n = 55) showed reproducible categories of responders (low, intermediate, and high). The binding of IL-2 to the IL-2R complex on human neutrophils increased on GM-CSF-stimulated neutrophils compared with unstimulated cells. However, no increase in the level of expression of either the alpha or beta chains of this receptor complex was observed. This finding suggests that GM-CSF functionally activates the IL-2R, but does not regulate its level of expression. Finally, we found that human neutrophils constitutively express IL-2R gamma chain mRNA and thus have the potential to express the functional IL-2R complex. Our findings on IL-2-neutrophil interactions should lead to new avenues of research in understanding the responses of patients undergoing GM-CSF or IL-2 therapy.     

Molecular Genetic Testing for Malignant Hyperthermia Susceptibility

Background: For more than 30 yr, the in vitro contracture test (IVCT) was the only appropriate diagnostic tool for malignant hyperthermia (MH). After the introduction of molecular genetics into MH research, guidelines for molecular genetic diagnosis of MH susceptibility were published. The aim of this study was to establish applicability of the guidelines, sensitivity, and specificity of genetic testing in MH and advantages for studied patients.

Methods: The IVCT was performed following the guidelines of the European MH Group. Mutation analyses were performed by amplification of genomic DNA by polymerase chain reaction and restriction enzyme digestion.

Results: Two hundred eight individuals underwent MH testing between January 2001 and April 2003. In 32 of 67 initially genetic-tested patients, the familial mutation was identified, and they were diagnosed as MH susceptible. The IVCT followed negative genetic test results in 20 patients, and all but one had negative IVCT results. Three patients were scheduled to undergo elective surgery, and IVCT and genetic testing were performed simultaneously. All three had positive IVCT results and were carriers of their familial mutation.     

Normal outcome after prenatal diagnosis of thrombosis of the torcular Herophili

We report a case of prenatal diagnosis of thrombosis of the torcular Herophili. Detection at 22 weeks' gestation by ultrasound scan of an anechoic mass located immediately above the tentorium led to magnetic resonance imaging (MRI) being performed at 28 weeks which established the diagnosis of an isolated thrombosis of the torcular Herophili. MRI remained stable throughout pregnancy, and postnatal MRI confirmed the diagnosis at 2.5 months of age. The child is now 16 months old and developing normally.     

Neoadjuvant chemoradiation in non-small cell lung cancer]

In 2006 preoperative chemoradiation is a major part of the treatment of stage III locally advanced non-small cell lung cancer. Previous studies have clearly demonstrated the feasibility both regarding toxicities and resectability rates of the sequential and concurrent combination of radiation to chemotherapy in a neoadjuvant setting. However, induction chemoradiation has never been randomly compared to exclusive preoperative chemotherapy. Besides, the doses of radiation and the optimal drug combination remain undetermined at the time. Regarding the global therapeutic strategy of stage III non-small cell lung cancer, recently reported phase III trials evaluating the role of surgical resection after induction chemotherapy or chemoradiation, all showed the prognostic importance of the tumoral and mediastinal downstaging to select patients really benefiting from surgery. These developments make of the treatment of locally advanced non-small cell lung cancer a model for multimodal therapeutic strategies combining chemotherapy, radiotherapy and surgery.     

Chemoradiation for locally advanced non-small cell lung cancer.]

Chemoradiation is one of the major therapeutic options in thoracic oncology: besides surgery, the best treatment for early-stage tumors, and chemotherapy, not only used in metastatic tumors, but also in a neoadjuvant and adjuvant setting, chemoradiation is the standard strategy for unresectable locally advanced non-small cell lung cancer. Its current modalities include three-dimensional conformal techniques, allowing dose escalation and sequential and concurrent combination with new generation cytotoxic agents to occur. Phase III trials are currently evaluating the benefit from induction and consolidation chemotherapy in this setting. New techniques of radiation may also increase the efficacy and the feasibility of radiation. This constant progress makes chemoradiation one of the most promising combined treatments in thoracic oncology.