Aflibercept Action in a Rabbit Model of Chronic Retinal Neovascularization: Reversible Inhibition of Pathologic Leakage With Dose-Dependent Duration.

Purpose: We establish and characterize the chronic retinal neovascularization (RNV) induced by intravitreal (IVT) injection of DL-α-aminoadipic acid (AAA) in a rabbit model and investigate the extent and duration of inhibitory actions induced by IVT aflibercept on the RNV.

Methods: Rabbits received a single IVT injection of AAA, with weekly follow-up fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT). After 10 weeks, they received a single IVT aflibercept or control injection.

Downmodulation of vaccine-induced immunity and protection against the intracellular bacterium Francisella tularensis by the inhibitory receptor FcγRIIB.

Fc gamma receptor IIB (FcγRIIB) is the only Fc gamma receptor (FcγR) which negatively regulates the immune response, when engaged by antigen- (Ag-) antibody (Ab) complexes. Thus, the generation of Ag-specific IgG in response to infection or immunization has the potential to downmodulate immune protection against infection. Therefore, we sought to determine the impact of FcγRIIB on immune protection against Francisella tularensis (Ft), a Category A biothreat agent.

Fc receptor-targeting of immunogen as a strategy for enhanced antigen loading, vaccination, and protection using intranasally administered antigen-pulsed dendritic cells.

Dendritic cells (DCs) play a critical role in the generation of adaptive immunity via the efficient capture, processing, and presentation of antigen (Ag) to naïve T cells. Administration of Ag-pulsed DCs is also an effective strategy for enhancing immunity to tumors and infectious disease organisms. Studies have also demonstrated that targeting Ags to Fcγ receptors (FcγR) on Ag presenting cells can enhance humoral and cellular immunity in vitro and in vivo.

Multiple mechanisms mediate enhanced immunity generated by mAb-inactivated F. tularensis immunogen.

We have previously demonstrated that immunization with the inactivated Francisella tularensis, a Category A intracellular mucosal pathogen, combined with IgG2a anti-F. tularensis monoclonal antibody (Ab), enhances protection against subsequent F. tularensis challenge.

Analysis of the molecular biologic milieu of the vitreous in proliferative vitreoretinopathy.

Purpose: Previous investigations have explored molecular differences between proliferative vitreoretinopathy and primary retinal detachment. An exploration of a greater number of molecules might provide novel insight into the biology of this disorder and identify potential therapeutic targets.

Methods: Vitreous specimens were obtained from patients with epiretinal membranes or macular puckers (n = 15), patients with a primary retinal detachment without proliferative vitreoretinopathy (n = 15), and patients with retinal detachments and proliferative vitreoretinopathy (n = 15).

Toll-like receptors in idiopathic orbital inflammation.

Purpose: A prior investigation has demonstrated that innate immune-specific cytokines are enriched in idiopathic orbital inflammation (IOI). To further document the role of innate immunity in IOI, the authors sought to determine whether toll-like receptors (TLRs) are present in biopsy specimens of this disorder.

Methods: Immunohistochemical staining for TLR2, TLR3, and TLR4 was performed on biopsy specimens taken from patients with IOI, and the number of TLR-positive cells was counted across five 40× light microscopic fields.

Molecular biologic assessment of cutaneous specimens of ocular rosacea.

Purpose: To characterize the molecular biologic environment of pathological skin in ocular rosacea and to differentiate the levels of inflammatory molecules in ocular rosacea from those of normal skin.

Methods: The concentrations of 48 molecules were assayed in cutaneous biopsies taken from patients with ocular rosacea and from normal controls.

Results: There were very few molecular differences between the 2 groups, and 43 of the 48 molecules that were measured in this study were not significantly different between the 2 groups.

Mucosal immunization with an unadjuvanted vaccine that targets Streptococcus pneumoniae PspA to human Fcγ receptor type I protects against pneumococcal infection through complement- and lactoferrin-mediated bactericidal activity.

Targeting an antigen to Fc receptors (FcR) can enhance the immune response to the antigen in the absence of adjuvant. Furthermore, we recently demonstrated that intranasal immunization with an FcγR-targeted antigen enhances protection against a category A intracellular mucosal pathogen, Francisella tularensis. To determine if a similar strategy could be applied to the important pathogen Streptococcus pneumoniae, we used an improved mucosal FcR-targeting strategy that specifically targets human FcγR type I (hFcγRI).

Characterization of the molecular biologic milieu of idiopathic orbital inflammation.

Purpose: To identify the cytokines that are expressed in elevated concentrations in idiopathic orbital inflammation (IOI).

Design: Experimental study.

Participants And Controls: Biopsy specimens from 8 patients with biopsy-proven IOI and negative serologic and radiographic examinations, versus orbital biopsy samples taken from 8 control patients without clinical evidence or subjective complaint of orbital inflammation.

Fc receptor-targeted mucosal vaccination as a novel strategy for the generation of enhanced immunity against mucosal and non-mucosal pathogens.

Numerous studies have demonstrated that targeting immunogens to Fcgamma receptors (FcgammaR) on antigen (Ag)-presenting cells (APC) can enhance humoral and cellular immunity in vitro and in vivo. FcgammaR are classified based on their molecular weight, IgG-Fc binding affinities, IgG subclass binding specificity, and cellular distribution and they consist of activating and inhibitory receptors. However, despite the potential advantages of targeting Ag to FcR at mucosal sites, very little is known regarding the role of FcR in mucosal immunity or the efficacy of FcR-targeted mucosal vaccines.

Computational identification of a p38SAPK-regulated transcription factor network required for tumor cell quiescence.

The stress-activated kinase p38 plays key roles in tumor suppression and induction of tumor cell dormancy. However, the mechanisms behind these functions remain poorly understood. Using computational tools, we identified a transcription factor (TF) network regulated by p38alpha/beta and required for human squamous carcinoma cell quiescence in vivo.

Expression pattern of glypican-3 (GPC3) during human embryonic and fetal development.

Glypicans represent a family of cell surface proteoglycans. Loss-of-function mutations in the human glypican-3 (GPC3) gene results in the Simpson-Golabi-Behmel syndrome, characterized by severe malformations and pre- and postnatal overgrowth. Because the expression of GPC3 during human embryonic and fetal periods remains largely unknown, we investigated by immunohistochemistry its pattern of expression during four periods of human development covering the embryonic period (P1) from 5 to 8 weeks of development, and the fetal periods (P2, P3 and P4) from 9 to 28 weeks of development.

Inhibition of proliferation by PERK regulates mammary acinar morphogenesis and tumor formation.

Endoplasmic reticulum (ER) stress signaling can be mediated by the ER kinase PERK, which phosphorylates its substrate eIF2alpha. This in turn, results in translational repression and the activation of downstream programs that can limit cell growth through cell cycle arrest and/or apoptosis. These responses can also be initiated by perturbations in cell adhesion.