Relative amounts of antagonistic splicing factors, hnRNP A1 and ASF/SF2, change during neoplastic lung growth: implications for pre-mRNA processing

Pre-mRNA processing is an important mechanism for globally modifying cellular protein composition during tumorigenesis. To understand this process during lung cancer, expression of two key pre-mRNA alternative splicing factors was compared in a mouse model of early lung carcinogenesis and during regenerative growth following reversible lung injury. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and alternative splicing factor/splicing factor 2 (ASF/SF2) act antagonistically to modulate splice site selection. Both hnRNP A1 and ASF/SF2 contents rose in adenomas and during injury-induced hyperplasia compared to control lungs, as measured by immunoblotting. While both proteins increased similarly during compensatory hyperplasia, hnRNP A1 increased to a much greater extent than ASF/SF2 in tumors, resulting in a 6-fold increase of the hnRNP A1 to ASF/SF2 ratio. Immunohistochemical analysis showed that hnRNP A1 localized exclusively within tumor nuclei, while ASF/SF2 appeared in cytoplasm and/or nuclei, depending on the growth pattern of the tumor cells. We also demonstrated cancer-associated changes in the pre-mRNA alternative splicing of CD44, a membrane glycoprotein involved in cell-cell and cell-extracellular matrix interactions. hnRNP A1 and ASF/SF2 expression is thus differentially altered in neoplastic lung cells by mechanisms that do not strictly arise from increased cell division. These changes are influenced by tumor histology and may be associated with production of variant CD44 mRNA isoforms

The shuttle walk test: a new approach to functional walking capacity measurements for patients after stroke?

Item does not contain fulltextOBJECTIVE: To determine the construct validity, test-retest reliability, and measurement error of the shuttle walk test (SWT) for patients after stroke. DESIGN: Clinimetric study. SETTING: Three rehabilitation centers in the Netherlands. PARTICIPANTS: A sample of patients after stroke (N=75; mean age +/- SD, 58.8+/-9.8y) who are capable of walking without physical assistance. Patients were excluded if they had sustained a subarachnoid hemorrhage or a stroke in the cerebellum or brainstem, or had any other conditions that limited their walking capacity more than the current stroke, or had sensory aphasia. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Construct validity (6-minute walk test [6MWT]) and test-retest reliability of the SWT were assessed. Measurement error was determined with the standard error of measurement (SEM), limits of agreement, and smallest detectable differences (SDDs). RESULTS: Construct validity was confirmed by high significant correlations (r(p)>/=.65, P/=0.8m/s). In the small group (n=12) of low-speed walkers (<0.8m/s), no significant correlations and differences between both tests were found except for walking distance in favor of the 6MWT. Test-retest reliability was good (intraclass correlation coefficient model 2,1 [ICC(2,1)]=.961 [.936-.977]). SEM was 6.0%, and the SDDs for individual and group were 302.0m (37%) and 38.7m (5%), respectively. CONCLUSIONS: The SWT is a valid and reliable measure and therefore a feasible instrument to determine functional walking capacity of patients after stroke, especially in high-speed walkers

A new model for large interconnected power systems planning studies A methodology applied to the east-west interconnection in Europe

SIGLEAvailable at INIST (FR), Document Supply Service, under shelf-number : 26165 B, issue : a.1997 n.5 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc