p16(INK4a), cyclin-dependent kinase inhibitor, is functionally inactivated in many tumors, including cervical cancer. We compared p16(INK4A) immunocytochemical staining and Hybrid Capture 2 (HCII) on SurePath specimens using tissue biopsies (as the gold standard). Their utility in a spectrum of atypical and preneoplastic lesions, and their ability to accurately identify underlying lesions of CIN II or greater was assessed using biopsy follow-up data. One-hundred and seventeen residual SurePath samples were collected: 43 atypical squamous cells of undetermined significance (ASCUS), 47 low-grade (LGSIL), and 27 high-grade (HGSIL) squamous intraepithelial lesions. Two slides were prepared from each sample; one stained with the SurePath autocyte stain and one immunostained using the CINtec p16(INK4a) Cytology Kit (Dakocytomation). High-risk HPV testing was performed using the HCII DNA test (Digene, Gaithersburg, MD). Available tissue biopsy follow-up data was retrieved. p16(INK4a) was positive in 32.6% (14/43) ASCUS, 46.8% (22/47) LGSIL, and 48.1% (13/27) HGSIL specimens. HCII DNA test was positive in 41.9% (18/43) ASCUS, 78.7% (37/47) LGSIL, and 96.3% (26/27) HGSIL samples. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of p16(INK4a) and HCII were: 58.7% and 89.8%, 58.6% and 34.6%, 69.2% and 72.1%, 47.2% and 64.3%, respectively. In patients with cervical biopsies, the PPV of HCII (92.3%) results for a biopsy with CINII/III was significantly higher than the PPV of p16(INK4a) (52%) (P=0.001). Using liquid-based cytology specimens, HCII is a more sensitive test than p16(INK4a) for detection of abnormal cytology. HCII has a higher PPV than p16(INK4a) for identifying CIN II/III.
Red blood cell (RBC) transfusions were requested for a 60-year-old woman with hypoplastic myelodysplastic syndrome (MDS) treated with cyclosporine to reverse progressive pancytopenia. During routine forward grouping, the patient typed as group A, but with mixed-field reactivity in the anti-A column of the gel card (Left panel, red box). Reverse typing with A1 and B cells in the right-most two gel columns was consistent with blood group A. Common causes of mixed-field agglutination were excluded, including transfusion within the last 3 months and the presence of A-subgroups.To further investigate the mixed-field result, we utilized an automated fluorescence cytometric blood typing method previously described by our group 1,2 (Right panel. The density of antigen expression [PE fluorescence] increases from left to right; isotype control [iso] is purified polyclonal IgM). These studies showed that the patient's RBCs were group A, but could be separated into two distinguishable subpopulations that differed in their levels of A antigen expression (red line). Note that the population on the left (dashed arrow), with lower PE fluorescence, nonetheless does express residual A antigen as it is shifted to the right of the isotype control reaction (blue line). The population on the right (solid arrow) shows more usual levels of A antigen expression. In agreement with the typing results on the gel card, the patient's RBCs were negative for B antigen (black line). Thus, the mixed-field reaction seen on the gel card was due to the loss of A-antigen expression on a subpopulation of the patient's RBCs-a phenomenon that has been described in MDS patients. In addition to routine blood typing 1,2 , fluorescence cytometry is a powerful method for resolving complicated immunohematologic problems.
Signal transduction is an essential process in cells. One critical signaling molecule, protein kinase A (PKA), phosphorylates target proteins, thereby changing their conformations and modifying their functions. PKA is a component of multiple signaling pathways that regulate a variety of proteins. Since the broad substrate specificity of PKA can lead to phosphorylation of unintended proteins, PKA activity must be limited to specific times and places. A‐kinase anchoring proteins (AKAPs) bind and help localize PKA to specific areas. The RIIa domain in PKA provides a shallow groove for an amphipathic helix of AKAP to bind via interactions of hydrophobic side chains. A similar binding motif is found in the DPY‐30 domain, which suggests this domain may also play a localization role. The ability of AKAP to interact with PKA and regulate its activity is essential for the specificity of many cellular responses. The ability of a cell to localize proteins containing a DPY‐30 domain may also be important for proper function. If localization is disrupted, serious problems like heart disease and cancer may result. To further understand the impact of structural interactions on localization, physical models of RIIa, DPY‐30, and AKAP amphipathic helix have been designed and built by the Cedarburg High School SMART (Students Modeling a Research Topic) Team using 3D printing technology. Supported by a grant from NIH‐NCRR‐SEPA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.