The molecular analysis of diagnostic tissue specimens has given significant insight into the pathogenesis of human disease and led to the identification of a broad range of diagnostic and prognostic markers, especially for neoplastic disorders. High-throughput approaches for the examination of DNA, mRNA, and proteins will have a profound impact on tissue-based diagnostics and will complement conventional histological examination. However, the reliability of many tests based on tissue or cell extracts critically depends on the abundance of the cell population in question. Primary tissues contain a variety of cellular elements including specialized, organotypic parenchyma and a large range of stromal and inflammatory cells. The relative percentages of these different cell types vary widely, especially in pathologically altered tissues. This inherent complexity of primary tissues can lead to false negative results in diagnostic molecular tests. Whereas the PCR detection threshold for some genetic alterations such as tumor-specific chromosomal translocations are in the range of 1 in 104 cells or less carrying the marker, other tests such as the detection of clonal immunoglobulin or T-cell receptor gene rearrangements with consensus primers or loss of heterozygosity at tumor suppressor gene loci require higher percentages of target cells. In addition, the examination of early or precursor lesions such as carcinoma in situ and epithelial dysplasias, which can shed light on the first seminal steps of carcinogenesis, is virtually impossible from bulk tissue extracts.

These problems are magnified at the mRNA and protein level, as, frequently, the relative abundance of the target, rather than its presence or absence, is of diagnostic relevance. In situ studies such as immuno-histochemistry and in situ hybridization provide valuable alternatives, but are limited in their application range. For these reasons, microdissection strategies, ranging from relatively crude, manual microdissection to micromanipulation of single cells, have been used increasingly for the isolation of pure cell populations from primary tissues.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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