We report a fully quantitative spectroscopy imaging instrument for wide area detection of early cancer (dysplasia). This instrument provides quantitative maps of tissue biochemistry and morphology, making it a potentially powerful surveillance tool for objective early cancer detection. We describe the design, construction, calibration, and first clinical application of this new system. We demonstrate its accuracy using physical tissue models. We validate its diagnostic ability on a resected colon adenoma, and demonstrate feasibility of in vivo imaging in the oral cavity.
Quantitative spectroscopy has recently been extended from a contact-probe to wide-area spectroscopic imaging to enable mapping of optical properties across a wide area of tissue. We train quantitative spectroscopic imaging (QSI) to identify cervical high-grade squamous intraepithelial lesions (HSILs) in 34 subjects undergoing the loop electrosurgical excision procedure (LEEP subjects). QSI's performance is then prospectively evaluated on the clinically suspicious biopsy sites from 47 subjects undergoing colposcopic-directed biopsy. The results show the per-subject normalized reduced scattering coefficient at 700 nm (An) and the total hemoglobin concentration are significantly different (p<0.05) between HSIL and non-HSIL sites in LEEP subjects. An alone retrospectively distinguishes HSIL from non-HSIL with 89% sensitivity and 83% specificity. It alone applied prospectively on the biopsy sites distinguishes HSIL from non-HSIL with 81% sensitivity and 78% specificity. The findings of this study agree with those of an earlier contact-probe study, validating the robustness of QSI, and specifically An, for identifying HSIL. The performance of An suggests an easy to use and an inexpensive to manufacture monochromatic instrument is capable of early cervical cancer detection, which could be used as a screening and diagnostic tool for detecting cervical cancer in low resource countries.
Calcitriol is the active form of Vitamin D 3. Epidemiological data show that women with Vitamin D deficiency at the time of breast cancer diagnosis are 94% more likely to experience cancer spread and 73% more likely to die over the next 10 years, compared to women with adequate Vitamin D levels. Since vitamin D deficiency is especially common in African American and obese women, this observation may partially explain the relatively poor clinical outcome experienced by these patients [2]. Although current treatments for IBC
stability of the employed oligonucleotide nanolevers under different electrolyte conditions. Temperature dependent data are presented from 4 to 70 C for a range of different bacterial and human proteins: while some show a straightforward unfolding transition, others feature more complex signatures which are indicative of the protein expansion before an unfolding of individual domains sets in at higher temperatures. We discuss the possibility to evaluate quantitative thermodynamic parameters (melting points, transition energies) from the molecular dynamics data and compare our results to established methods like thermofluor assays. Since the presented approach works on a chip surface it uses minimal amounts of sample and can be performed in parallel using a microelectrode array. In addition, it yields binding kinetics data (association and dissociation rates) and affinity values and thus is ideally suited for investigating interactions in combination with a thermodynamic characterization of the involved proteins.
Dense protein complexes such as those found in the immunological synapses of antigen-activated lymphocytes are sites of critical biological activity, but their study is complicated by the large number of protein species present. Array tomography is a proteomic imaging method capable of addressing this highdimensional problem through iterative immunostaining, but would be difficult to apply to spatially-restricted regions of interest such as complexes within the immunological synapse that form in the area of contact between lymphocytes and antigen-presenting surfaces. We have developed a novel variant of this technique which embeds a thin (~500 nm) slice of material in LR White, making proteomic multiplexing possible. We are using this method with physically unroofed resting and activated B cells to study signaling in antigen-receptor microclusters in B cell plasma membranes. Here we present this method, and our current work in its application to the B cell membrane.
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