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101.
102.
The search for biomarkers is driven by the increasing clinical importance of early diagnosis. Reliable biomarkers can also assist in directing therapy, monitoring disease activity and the efficacy of treatment. In addition, the discovery of novel biomarkers might provide clues to the pathogenesis of a disease. The dynamic range of protein concentrations in body fluids exceeds 10 orders of magnitude. These huge differences in concentrations complicate the detection of proteins with low expression levels. Since all classical biomarkers have low expression levels (e.g., prostate-specific antigen: 2-4 microg/l; and CA125: 20-35 U/ml), new developments with respect to identification and validation techniques of the low-abundance proteins are required. This review will discuss the current status of profiling cerebrospinal fluid using mass spectrometry-based techniques, and new developments in this area.  相似文献   
103.
Although the cause of pre-eclampsia during pregnancy has not been elucidated yet, it is evident that placental and maternal endothelial dysfunction is involved. We previously demonstrated that in early onset pre-eclampsia placental calcyclin (S100A6) expression is significantly higher compared to controls ( De Groot , C. J. ; Clin. Proteomics 2007 , 1 , 325 ). In the current study, the results were confirmed and relatively quantified by using multiple reaction monitoring (MRM) on two peptide fragments of calcyclin. Cells were obtained from control (n = 5) and pre-eclamptic placental (n = 5) tissue collected by laser capture microdissection from formalin-fixed paraffin-embedded (FFPE) material treated with a solution to reverse formalin fixation. Two calcyclin peptides with an extra glycine inserted in the middle of the amino acid sequence were synthesized and used as an internal reference. Data presented show that MRM on laser microdissected material from FFPE tissue material is possible. The developed MRM assay to study quantitative levels of proteins in FFPE laser microdissected cells using nonisotopic-labeled chemical analogs of mass tagged internal references showed that in pre-eclamptic patients elevated levels of calcyclin is observed in placental trophoblast cells compared to normal trophoblast cells. By immunohistochemistry, we were able to confirm this observation in a qualitative manner.  相似文献   
104.
The adenovirus-2 major late promoter (Ad2MLP) upstream element (Ad2MLP-UE) contains a sequence of interrupted dyad symmetry. By inverting this element we have found that it functions in a bidirectional manner both in vivo and in vitro. Footprinting and binding kinetics studies have demonstrated that both orientations of the upstream element bind the sequence-specific upstream factor (UEF) in a similar fashion. These data strongly suggest that the dyad symmetric sequence is sufficient for fully functional binding of the UEF. Binding studies of the UEF to the Ad2MLP-UE indicate that, contrary to prokaryotic palindromic promoter elements which bind multimers of specific factors, the entire Ad2MLP dyad symmetric upstream element binds a single monomeric UEF molecule.  相似文献   
105.
This article argues that traditional models of diagnosis are incomplete in their reliance on a models of certainty that are no longer tenable in a postmodern world. Further, it argues that the current form of diagnosis, as applied to psychiatric and affective disorders, reduces patient agency and reinscribes the effects of biopower.  相似文献   
106.
Six fiber types have been described in the ambiens muscle of red-eared turtles. These include one slow oxidative type, two fast oxidative types, two fast oxidative and glycolytic types, and one fast glycolytic type. Fiber types are non-randomly distributed throughout cross sections of the muscle. There is a decreasing gradient of oxidative staining and an increasing gradient of glycolytic staining along an axis from the superficial to deep regions of the muscle. The slow oxidative fibers are predominantly located within one or two fascicles of the superficial surface of the muscle. The fast glycolytic fibers are predominant in deep fascicles. In contrast to previous reports of histochemically monotypic intrafusal fibers in turtle muscle, ambiens muscle spindles have been observed containing one to eleven intrafusal fibers, including two fiber types. Fiber diameter and area are consistently smaller than observed in most extrafusal fibers. Spindles are predominantly located in superficial and cranial fascicles of the ambiens muscle and are located in regions characterized by extrafusal fibers with high oxidative activity.  相似文献   
107.
The relation between dose, systemic availability, and response to oral debrisoquine was studied in 13 hypertensive patients receiving no other treatment. In 11 who received the same daily dose (40 mg) the fall in mean standing systolic blood pressure varied between 0-3 and 44-4 mm Hg. There was a ninefold difference in the daily urinary excretion and pre-dose plasma concentration of unchanged drug but an inverse correlation between daily urinary excretion of debrisoquine and its 4-hydroxy metabolite (r= -0-86), suggesting that a low recovery of debrisoquine occurs because of extensive metabolism. There was a significant correlation between the fall in standing systolic blood pressure and the mean daily urinary excretion (r= +0-82) and pre-dose plasma concentration (r= +0-82) of unchanged debrisoquine. In contrast, there was a significant inverse correlation between the urinary recovery of the metabolite and the fall in blood pressure (r= -0-82). The availability of debrisoquine is the major determinant of response to this drug. In the absence of side effects a poor response may be an indication to increase the daily dose rather than add another hypotensive agent.  相似文献   
108.

Background  

Statistical comparison of peptide profiles in biomarker discovery requires fast, user-friendly software for high throughput data analysis. Important features are flexibility in changing input variables and statistical analysis of peptides that are differentially expressed between patient and control groups. In addition, integration the mass spectrometry data with the results of other experiments, such as microarray analysis, and information from other databases requires a central storage of the profile matrix, where protein id's can be added to peptide masses of interest.  相似文献   
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