PURPOSE. To estimate visual field (VF) sensitivity at which retinal nerve fiber layer (RNFL) thinning reaches the measurement floor and at which RNFL stops thinning (change points), the dynamic range of RNFL thickness, and the number of steps from normal to RNFL floor among three optical coherence tomography (OCT) devices.
METHODS.Glaucomatous patients (n ¼ 58) and healthy subjects (n ¼ 55-60) prospectively underwent VF testing and RNFL thickness measurement with Cirrus, Spectralis, and RTVue. Change points and corresponding RNFL thicknesses were estimated with simple linear regression (SLR) and Bayesian change point (BCP) analyses. The dynamic range and number of steps to RNFL floor were determined.RESULTS. The average VF change points and corresponding residual thickness at the time RNFL stopped thinning were À22.2 dB and 57.0 lm (Cirrus), À25.3 dB and 49.2 lm (Spectralis), and À24.6 dB and 64.7 lm (RTVue). The RNFL dynamic ranges derived from SLR values were wider on Spectralis (52.6 lm) than on Cirrus (35.4 lm) and RTVue (35.5 lm); the corresponding number of steps to reach the RNFL floor were 9.0 on Cirrus, 10.6 on Spectralis, and 8.3 on RTVue.CONCLUSIONS. The relative VF sensitivity at which average RNFL thickness reaches the measurement floor, the residual layer thickness, and RNFL dynamic measurement range differ among the three devices. However, the number of steps from normal to the RNFL thickness floor is comparable.
Delivery to the proper tissue compartment is a major obstacle hampering the potential of cellular therapeutics for medical conditions. Delivery of cells within biomaterials may improve localization, but traditional and newer void‐forming hydrogels must be made in advance with cells being added into the scaffold during the manufacturing process. Injectable, in situ cross‐linking microporous scaffolds are recently developed that demonstrate a remarkable ability to provide a matrix for cellular proliferation and growth in vitro in three dimensions. The ability of these scaffolds to deliver cells in vivo is currently unknown. Herein, it is shown that mesenchymal stem cells (MSCs) can be co‐injected locally with microparticle scaffolds assembled in situ immediately following injection. MSC delivery within a microporous scaffold enhances MSC retention subcutaneously when compared to cell delivery alone or delivery within traditional in situ cross‐linked nanoporous hydrogels. After two weeks, endothelial cells forming blood vessels are recruited to the scaffold and cells retaining the MSC marker CD29 remain viable within the scaffold. These findings highlight the utility of this approach in achieving localized delivery of stem cells through an injectable porous matrix while limiting obstacles of introducing cells within the scaffold manufacturing process.
Three polypeptides are produced from the major immediate-early (IE) region of human cytomegalovirus by alternative splicing. The IE gene products regulate subsequent viral and cellular gene expression. We previously reported that cotransfection of a genomic clone of the major IE region stimulated transient expression of chloramphenicol acetyltransferase driven by the dihydrofolate reductase (DHFR) promoter and that an intact E2F site was required for the trans activation (M. Wade, T. F. Kowalik, M. Mudryj, E.-S. Huang, and J. C. Azizkhan, Mol. Cell. Biol. 12:4364-4374, 1992). With the availability of cDNA clones for the individual major IE proteins, we sought to determine which of these proteins exerted this effect and whether the IE protein(s) interacted with E2F. In this study, we use cotransfection to demonstrate that the 55-and 86-kDa major IE proteins from the IE2 region can each moderately trans activate the DHFR promoter and that the 72-kDa IE1 protein stimulates DHFR transcription to a much higher level. Furthermore, trans activation through the 72-kDa IE1 protein is in part E2F dependent, while activation by the 55-and 86-kDa IE proteins is E2F independent. We also demonstrate by in vitro pull-down assays that the 72-kDa IE1 protein can specifically interact with the DNA binding domain of E2F1 (amino acids 88 to 191) in the presence of nuclear extract. Moreover, antibodies to either E2F1 or IE72 will immunoprecipitate both E2F and IE72 from cells that stably express IE72, and antibody to E2F1 will immunoprecipitate IE72 from normal human fibroblast cells infected with human cytomegalovirus.
Recognition of green disease is of paramount importance in diagnosing and treating glaucoma. Understanding the limitations of imaging technologies coupled with evaluation of serial OCT analyses, prompt clinical examination, and structure-function correlation is important to avoid missing real glaucoma requiring treatment.
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