The study was a prospective observational study comparing semiautomated to manual quantitative ultrasound biomicroscopy image analysis among 82 images from 41 eyes of 32 subjects (21 controls and 11 glaucoma) enrolled in the Pediatric Anterior Segment Imaging Innovation Study. Intraclass correlation coefficients and correlation coefficients were >0.8 for all parameters, and comparison of respective analysis speed was 7 times faster for the semiautomated method compared with manual image quantification.
Objective: To identify corneal structure differences on quantitative high-frequency ultrasound biomicroscopy (UBM) among subjects with congenital glaucoma compared with controls. Methods: This prospective case–control study evaluated 180 UBM images from 44 eyes of 30 subjects (18 control and 12 glaucoma, mean age 5.2±8.0 years, range 0.2–25.8 years) enrolled in the Pediatric Anterior Segment Imaging and Innovation Study (PASIIS). ImageJ was used to quantify a comprehensive set of corneal structures according to 21 quantitative parameters. Statistical analysis compared corneal measurements in glaucoma subtypes and age-matched controls with significance testing and mixed effects models. Results: Significant differences between congenital glaucoma cases and controls were identified in 16 of 21 measured parameters including angle-to-angle, central and peripheral corneal thicknesses, scleral integrated pixel density, anterior corneal radius of curvature, and posterior corneal radius of curvature. Eight parameters differed significantly between primary congenital glaucoma and glaucoma following congenital cataract surgery. Conclusion: Multiple measurable corneal structural differences exist between congenital glaucoma and control eyes, and between primary and secondary congenital glaucoma, including but not limited to corneal width and thickness. The structural differences can be quantified from UBM image analysis. Further studies are needed to determine whether corneal features associated with glaucoma can be used to diagnose or monitor progression of congenital glaucoma.
Abstract Natural killer T (NKT) cells are important in antitumor immunity, but these cells are significantly reduced in breast cancer (BC) patients. The tumor-associated factors that lead to the reduction in NKT cells are unclear; however, it is known that during malignancy BCs upregulate pro-survival proteins in order to proliferate and evade immune detection. Cell Cycle and Apoptosis Regulatory Protein (CARP)-1, a perinuclear phosphoprotein that regulates cell growth and apoptosis, is overexpressed in chemotherapy-treated cancers and several BC cell lines, such as MCF-7. CARP functional mimetics (CFMs) are small molecule inhibitors that interfere with the interaction of CARP-1 and the anaphase promoting complex, causing cell cycle arrest and apoptosis. Thus, we hypothesize that targeting CARP-1 through the use of CFMs will induce apoptosis and restore anti-tumor immune responses. In this study, BC cell lines were treated with CFM-4&5 and proliferation, cytotoxicity, and immunogenicity were assessed. It was found that pretreatment of human MCF-7 and murine E0771 BC lines with 20μM CFM-4&5 resulted in 80–100% cell death within 48–72h. In order to assess immunogenicity in the absence of cytotoxicity, BC cell lines were pretreated with 10μm for 24h, washed and cultured in fresh medium. Conditioned medium was collected and used to treat CD1d-expressing cells for 4h prior to coculture with NKT cell hybridomas. To test the effects of CFMs on immune cell activation, peripheral blood mononuclear cells (PBMC) from healthy and BC patients were treated with CFM-4&5 in the presence of stimuli and immuno-activity was assessed by ELISA. Collectively, these data implicate a novel role for targeting CARP-1 for the treatment of BC.
