Smoking and human airway inflammatory cells : studies with focus on T cells in the development of COPD

Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death worldwide, is characterized by persistent airflow limitation and a chronic inflammation of the lungs. One of the major risk factors is long-term exposure to cigarette smoking. The key inflammatory cells in the pathogenesis of COPD are macrophages, neutrophils and CD8+ T lymphocytes. The heterogeneity of COPD and the need for identifying patient subgroups is becoming increasingly recognized. Besides, the differences in the immunopathology of current- and exsmokers with COPD are uncertain. Characterizing the inflammatory mechanisms driving the disease in different subtypes of patients, including differences between men and women, will likely aid diagnostic procedures and tailoring of treatment strategies and caretaking. To investigate the airway and systemic inflammatory profile and the role for T cells in smoke-induced inflammation and COPD, bronchoalveolar lavage (BAL) fluid, blood and chest high resolution computed tomograpthy (HRCT) scans were collected from a genderand age-matched cohort of 40 never-smokers, 40 smokers with normal lung function and 38 COPD patients (27 current smokers and 11 ex-smokers). BAL characteristics, including the distribution of inflammatory cells, were assessed. T cells subsets in BAL and blood were phenotyped using flow cytometry, and the levels of cytokines, chemokines and growth factors in BAL fluid were assessed with a multi-plex bead-based assay. HRCT images of the lungs were analyzed for the investigation of morphological patterns and correlated with the cellular inflammatory patterns of the lungs. In addition to univariate analysis, multivariate data analysis with OPLS-modeling was used for discovering within- and between group variations, and potential biomarkers. The frequencies of several T cell subsets, including CD8+ T cells and NKT-like cells, both with cytotoxic capacities, and CD103+CD8+ T cells, were increased in BAL from smokers, regardless of airway obstruction. In COPD ex-smokers, the levels were similar to those of never-smokers. A more detailed phenotypic characterization of T cells revealed subsets specifically altered in smokers with normal lung function or COPD patients, including FOXP3+ regulatory T cells. A type 1 T cell-driven inflammation was indicated for female, but not male, COPD patients. Lung density, as measured by HRCT, was higher in smokers compared to both never-smokers and COPD patients and correlated with the cellular inflammation in the lungs. Taken together, these findings suggest that current smoking status has a larger impact on the distribution of lymphocytes in BAL than does airway obstruction. A detailed characterization of T cell subsets is important for finding disease-specific alterations. Gender-specific differences among smokers and COPD patients can be detected on a cellular level

Quantitative Pathology: Historical Background, Clinical Research and Application of Nuclear Morphometry and DNA Image Cytometry

Quantitative analysis of histo- and cytochemical components such as DNA, RNA or chromatin pattern on one hand (cytometry) and the quantitative analysis of geometric non-chemical cell and tissue components (morphometry and sterology) on the other, have developed somewhat independently. Today, many different techniques, such as morphometry, sterology, and static image and flow cytometry are well established and routinely used in diagnostic quantitative pathology. The potential significance of these techniques in the individualization of care in cancer patients include the objective distinction between benign, borderline and malignant lesions, objective grading of invasive tumours, prediction of prognosis, and therapy response

Diversity and Distribution of Mites (Acari: Ixodida, Mesostigmata, Trombidiformes, Sarcoptiformes) in the Svalbard Archipelago

Svalbard is a singular region to study biodiversity. Located at a high latitude and geographically isolated, the archipelago possesses widely varying environmental conditions and unique flora and fauna communities. It is also here where particularly rapid environmental changes are occurring, having amongst the fastest increases in mean air temperature in the Arctic. One of the most common and species-rich invertebrate groups in Svalbard is the mites (Acari). We here describe the characteristics of the Svalbard acarofauna, and, as a baseline, an updated inventory of 178 species (one Ixodida, 36 Mesostigmata, 43 Trombidiformes, and 98 Sarcoptiformes) along with their occurrences. In contrast to the Trombidiformes and Sarcoptiformes, which are dominated in Svalbard by species with wide geographical distributions, the Mesostigmata include many Arctic species (39%); it would thus be an interesting future study to determine if mesostigmatid communities are more affected by global warming then other mite groups. A large number of new species (42 spp.) have been described from Svalbard, including 15 that have so far been found exclusively there. It is yet uncertain if any of these latter species are endemic: six are recent findings, the others are old records and, in most cases, impossible to verify. That the Arctic is still insufficiently sampled also limits conclusions concerning endemicity.publishedVersio

Genomic instability and proliferative activity as risk factors for distant metastases in breast cancer

The role of genomic instability and proliferative activity for development of distant metastases in breast cancer was analysed, and the relative contribution of these two risk factors was quantified. A detailed quantitative comparison was performed between Ki67 and cyclin A as proliferative markers. The frequency of Ki67 and cyclin A-positive cells was scored in the same microscopic areas in 428 breast tumours. The frequency of Ki67-positive cells was found to be highly correlated with the frequency of cyclin A-positive cells, and both proliferation markers were equally good to predict risk of distant metastases. The relative contribution of degree of aneuploidy and proliferative activity as risk markers for developing distant metastases was studied independently. Although increased proliferative activity in general was associated with an increased risk of developing distant metastases, ploidy level was found to be an independent and even stronger marker when considering the group of small (T1) node negative tumours. By combining proliferative activity and ploidy level, a large group of low risk breast tumours (39%) could be identified in which only a few percentage of the tumours (5%) developed distant metastases during the 9-year follow-up time period

Imagination and narrative : young people's experiences

Imagery generation in dramatized audio drama is still poorly understood with the majority of work having been done from a radio advertising perspective. This study sought to understand audio drama imagery generation by using teenage listeners. The study demonstrated that teenagers can follow purely auditory narrative with ease and can generate unique and vivid imagery through aural dramatic stimulation. The study also showed that listening in the dark and as a group are appealing for audiences

A Role for Polyploidy in the Tumorigenicity of Pim-1-Expressing Human Prostate and Mammary Epithelial Cells

Polyploidy is a prominent feature of many human cancers, and it has long been hypothesized that polyploidy may contribute to tumorigenesis by promoting genomic instability. In this study, we investigated whether polyploidy per se induced by a relevant oncogene can promote genomic instability and tumorigenicity in human epithelial cells.When the oncogenic serine-threonine kinase Pim-1 is overexpressed in immortalized, non-tumorigenic human prostate and mammary epithelial cells, these cells gradually converted to polyploidy and became tumorigenic. To assess the contribution of polyploidy to tumorigenicity, we obtained sorted, matched populations of diploid and polyploid cells expressing equivalent levels of the Pim-1 protein. Spectral karyotyping revealed evidence of emerging numerical and structural chromosomal abnormalities in polyploid cells, supporting the proposition that polyploidy promotes chromosomal instability. Polyploid cells displayed an intact p53/p21 pathway, indicating that the viability of polyploid cells in this system is not dependent on the inactivation of the p53 signaling pathway. Remarkably, only the sorted polyploid cells were tumorigenic in vitro and in vivo.Our results support the notion that polyploidy can promote chromosomal instability and the initiation of tumorigenesis in human epithelial cells

Prognostic factors in prostate cancer

Prognostic factors in organ confined prostate cancer will reflect survival after surgical radical prostatectomy. Gleason score, tumour volume, surgical margins and Ki-67 index have the most significant prognosticators. Also the origins from the transitional zone, p53 status in cancer tissue, stage, and aneuploidy have shown prognostic significance. Progression-associated features include Gleason score, stage, and capsular invasion, but PSA is also highly significant. Progression can also be predicted with biological markers (E-cadherin, microvessel density, and aneuploidy) with high level of significance. Other prognostic features of clinical or PSA-associated progression include age, IGF-1, p27, and Ki-67. In patients who were treated with radiotherapy the survival was potentially predictable with age, race and p53, but available research on other markers is limited. The most significant published survival-associated prognosticators of prostate cancer with extension outside prostate are microvessel density and total blood PSA. However, survival can potentially be predicted by other markers like androgen receptor, and Ki-67-positive cell fraction. In advanced prostate cancer nuclear morphometry and Gleason score are the most highly significant progression-associated prognosticators. In conclusion, Gleason score, capsular invasion, blood PSA, stage, and aneuploidy are the best markers of progression in organ confined disease. Other biological markers are less important. In advanced disease Gleason score and nuclear morphometry can be used as predictors of progression. Compound prognostic factors based on combinations of single prognosticators, or on gene expression profiles (tested by DNA arrays) are promising, but clinically relevant data is still lacking