Primitive streak formation in the chick embryo involves large scale highly coordinated flows of over 100.000 cells in the epiblast. These large scale tissue flows and deformations can be correlated with specific anisotropic cell behaviours in the forming mesendoderm through a combined light-sheet microscopy and computational analysis. Relevant behaviours include apical contraction, elongation along the apical-basal axis followed by ingression as well as asynchronous directional cell intercalation of small groups of mesendoderm cells. Cell intercalation is associated with sequential, directional contraction of apical junctions, the onset, localisation and direction of which correlate strongly with the appearance of active Myosin II cables in aligned apical junctions in neighbouring cells. Use of a class specific Myosin inhibitors and gene specific knockdowns show that apical contraction and intercalation are Myosin II dependent and also reveal critical roles for Myosin I and Myosin V family members in the assembly of junctional Myosin II cables.

Objectives This study attempts to estimate the proportion of annual deaths related to occupational factors in Finland and considers related methodological issues and associated uncertainties.Methods Statistics on causes of death, numbers of subjects exposed, and risk ratios obtained from the epidemiologic literature were used to estimate the population attributable fraction and disease burden for causes of death from work-related diseases. Gender-, age-and disease-specific numbers of deaths were provided by Statistics Finland for 1996. Information on the size of the population, broken down by gender, age, occupation, and industry, was acquired from population censuses. A Finnish job-exposure matrix supplied data on the prevalence of exposure for specific agents and the level of exposure among exposed workers. ResultsThe attributable fraction of work-related mortality in the relevant disease and age categories was estimated to be 7% (10% for men and 2% for women), and for all diseases and ages the fraction was 4%. For the main cause-of-death categories, the attributable fraction became 12% for circulatory system diseases, 8% for malignant neoplasms, 4% for respiratory system diseases, 4% for mental disorders, 3% for nervous system diseases, and 3% for accidents and violence. The following estimates were obtained for specific important diseases: 24% for lung cancer, 17% for ischemic heart disease, 12% for chronic obstructive pulmonary disease, and 11% for stroke. Based on these fractions, the total number of work-related deaths that occurred in Finland in 1996 was calculated to be on the order of 1800 (employed work force of 2.1 million); 86% involved men.Conclusions High-quality epidemiologic studies and national survey data are essential for obtaining reliable estimates of the proportion of deaths attributable to occupational factors. The magnitude of work-related mortality is an insufficiently recognized contributor to total mortality in Finland, especially from circulatory diseases and other diseases caused by exposure to agents other than asbestos.Key terms attributable fraction, burden of disease, epidemiologic methods, health statistics, occupational exposure. Global estimates of the burden of disease due to occupational factors have been calculated through the application of Finnish rates of registered work-related diseases (1). The approach is subject to the following two fundamental uncertainties: (i) the validity of the data on disease incidence from the national reporting scheme and (ii) the validity of worldwide extrapolations to different regions with different exposure circumstances. With the exception of studies using workers' compensation records, only a few research projects have estimated the magnitude of morbidity or mortality induced by exposure to hazardous agents or stress factors in the work environment at a state or national level. The investigations conducted in this area have covered New York State (2), the whole of the United States (3), Canada (4), and Australia (5). Given the lack of ...

High mobility group A (HMGA) proteins play an important role in the regulation of transcription, differentiation, and neoplastic transformation. In this work, the expression of HMGA 1 and 2 in 152 lung carcinomas of mainly non-small-cell histological type has been studied by immunohistochemistry in order to evaluate their feasibility as lung cancer markers. In 17 lung cancer cases, the related bronchial epithelial changes were also studied for HMGA1 and 2 expression. RNA expression of HMGA1a and b isoforms and of HMGA2 was determined by real-time semi-quantitative RT-PCR in 23 lung carcinomas. High expression of HMGA1 and HMGA2 at both mRNA and protein levels was detected in lung carcinomas, compared with normal lung tissue. Nuclear immunostaining for HMGA1 and 2 proteins also occurred in hyperplastic, metaplastic, and dysplastic bronchial epithelium. Increased nuclear expression of HMGA1 and 2 correlated with poor survival (for adenocarcinomas, HMGA1, p=0.006; HMGA2, p=0.05). While the expression of HMGA2 was significantly associated with cell proliferation (p=0.008), HMGA1 expression did not show any association with proliferation or apoptotic index. Sequencing of HMGA2 transcripts from tumours with very high expression showed a normal full-length transcript. As HMGA proteins were expressed in about 90% of lung carcinomas and their expression was inversely associated with survival, they may provide useful markers for lung cancer diagnosis and prognosis.

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There are no population-based follow-up studies to estimate the fraction of asthma incidence that is attributable to work. In Finland, individuals with clinically well-established persistent asthma are registered for reimbursement of medication from the national health insurance scheme. We combined, at an individual level, these data with the population census data of 1985, 1990, and 1995 to estimate the attributable fraction of work in adult-onset persistent asthma. Our follow-up study covered the entire 25- to 59-yr-old employed population of Finland in 1986-1998. Relative risks (RR) for occupational categories were estimated in comparison to those employed in administrative work. There were 49,575 incident cases of asthma. The attributable fraction of occupation was 29% (95% CI 25-33%) for men and 17% (95% CI 15-19%) for women. The risk was increased especially in agricultural work, manufacturing work, and service work. In addition to already established risk occupations of occupational asthma, such as food and beverage work, the analysis identified a large number of occupations with significant excess of asthma incidence. The results indicate that the impact of occupational factors in the inception of adult-onset persistent asthma, and consequently the potential for prevention, is much larger and more widely spread than generally assumed.