Tissue bias

Figure 1 Bias in the chemokine system and other 7TMRs. Biased signaling describes the ability of a receptor to induce different signaling pathways or cellular events. Thereby, different ligands may activate different pathways via the same receptor (ligand bias, A), or the same ligand induces different outcomes at different receptors (receptor bias, B). Also the cell or tissue that "hosts" the ligand receptor interaction can modulate the induced signaling pathway (tissue bias, C).

These examples emphasize the need to consider tissue bias when planning assays or comparing results. Furthermore, due to the influence of the tissue or cell on the signaHng outcome, bias of any Hgand or receptor always... 

Second generation COMT inhibitors were developed by three laboratories in the late 1980s. Apart from CGP 28014, nitrocatechol is the key structure of the majority of these molecules (Fig. 3). The current COMT inhibitors can be classified as follows (i) mainly peripherally acting nitrocatechol-type compounds (entacapone, nitecapone, BIA 3-202), (ii) broad-spectrum nitrocatechols having activity both in peripheral tissues and the brain (tolcapone, Ro 41-0960, dinitrocatechol, vinylphenylk-etone), and (iii) atypical compounds, pyridine derivatives (CGP 28014,3-hydroxy-4-pyridone and its derivatives), some of which are not COMT inhibitors in vitro but inhibit catechol O-methylation by some other mechanism. The common features of the most new compounds are excellent potency, low toxicity and activity through oral administration. Their biochemical properties have been fairly well characterized. Most of these compounds have an excellent selectivity in that they do not affect any other enzymes studied [2,3]. 

In summary, studies carried out with tissue surrogates25 highlight some of the problems that must be overcome before proteins extracted from FFPE tissues can be used for routine proteomic studies. First, these studies demonstrate that reversal of protein-formaldehyde adducts does not assure quantitative extraction of proteins from FFPE tissues or vice-versa. It may ultimately turn out that there is no one universal method that can accomplish both tasks, but that instead, each step will need to be optimized separately. Studies with tissue surrogates also suggest that failure to quantitatively extract the entire protein component from FFPE tissues may result in sampling bias due to the preferential extraction of certain proteins. This behavior may be linked to protein physical properties, such as the isoelectric point. The results of our... 

BIA is a simple, noninvasive, and relatively inexpensive way to measure LBM. It is based on differences between fat tissue and lean tissue s resistance to conductivity. Fluid status should be considered in interpretation of BIA results. 

In view of these complexities, environmental studies that seek to verify proposed cause-effect relationships between contamination and response need to be carefully designed to avoid bias and misunderstanding. Most environmental assessments adopt a multi-tiered approach to testing, in which combinations of biological responses (biomarkers) are measured in tissue samples, body fluids or at the whole organism level to indicate exposure to or adverse effects of contamination.8. Auffret and colleagues60 surveyed Pacific oysters from the Atlantic coast of Brittany after the Erika oil spill between... 

The cardenolides in the larval hemolymph are about at an equivalent concentration with those distributed in the other larval tissues, negligible amounts of these steroids being present in the gut (26). In the adult, cardenolides are equally distributed between the three main body regions and the wings, with females containing about twice as much of these steroids as males. This female bias in cardenolide concentration appears to be directly attributable to the presence of substantial amounts of these steroids in the eggs. 

Bia was the most abundant residue representing 78.3% of the total residues, the eprinomectin Bib 8.3%, tire 24a-hydroxymethyl metabolite 7.4%, whereas the sum of the minor 24a-hydroxy-, 26a-hydroxymethyl-, and 7V-deacetylated metabolites represented less than 1.6%. The metabolism profile also indicated that eprinomectin Bj was the major residue in all edible tissues, the eprinomectin Bib representing 7.2-9.3%, whereas five to seven minor metabolites represented only 1-2% of tire total radioactivity. In muscle, however, the 7V-deacetylated metabolite accounted for as much as 3.9% of the total residues. Eprinomectin Bia was also found to be a major metabolite, accounting for 80-85.6% of the total extractable radioactivity in milk. In this matrix, the 24a-hydroxymethyl metabolite represented less than 2%, Ure N-deacetylated metabolite 0,7-2.5%, whereas the contribution by Ure other metabolites was negligible. 

These investigations have shown significant associations with several types of cancer, but the most consistent findings have been for soft-tissue sarcoma and non-Hodgkin lymphoma. Although the odds ratios in some case-control studies may have been inflated by recall bias, this cannot explain all of the findings. Nor are they likely to have arisen by chance. It is not possible, however, to exclude a confounding effect of polychlorinated dibenzo-para-dioxins which occur as contaminants in chlorophenols. 

Persikov, A. V., Pillitteri, R. J., Amin, P., Schwarze, U., Byers, P. H., and Brodsky, B. (2004). Stability related bias in residues replacing glycines within the collagen triple helix (Gly-Xaa-Yaa) in inherited connective tissue disorders. Hum. Mut. 24, 330-337. 

TCDD and exact levels of exposure were not known. Furthermore, in some studies the exposure data were based solely on questionnaires and some recall bias could have been present. Other studies suffered from examining small cohorts or investigating the effects after a short latency period. The long latency period is important for detecting increases in soft-tissue sarcomas, presumably a major cancer outcome of CDD exposure in humans. 

While in vivo 19F MR has provided unique insight into fluoropyrimidine metabolism, most spectroscopic studies have limited numbers of patients and thus are subject to potential bias due to the variability in individual biometabolism. The small number of subjects can further limit generalization of the results to a larger population. In addition, studies of deep tissues or small lesions are challenging using 19F MR spectroscopy because they cannot be adequately evaluated using surface coil techniques and the low signal levels preclude use of a volume coil. 

Usually we are concerned to get a sample that is representative of the whole of a bulk material, or a fluid or a tissue. Sampling has to take account of the fact that only a small amount of sample is collected from a relatively vast bulk. Often it is necessary to take a number of random samples throughout the material. Any portion of the material represented by the sample must have an equal chance of being included. If we sample only from the parts that are easy to reach, we may be introducing bias. 

Although the vast majority of NMR metabolomics experiments are carried out in the liquid state, the analysis of intact tissue is made possible by solid-state NMR. This technique offers the obvious advantage of simple sample preparation and removes bias associated with differential solubility of metabolites. Magic angle... 

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