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Mount Sinai, NY, United States

Suzuki K.,Institute of Advanced Medicine | Yokoyama C.,Institute of Advanced Medicine | Higashi Y.,Institute for Developmental Research | Daikoku T.,University of Cincinnati | And 3 more authors.
Ocular Surface | Year: 2012

Epithelial-mesenchymal interactions and epithelial-to-mesenchymal transition (EMT) are essential during tissue formation and organ morphogenesis. The roles of Wnt/β-catenin signaling have been studied in many organ systems. In this review, we describe the importance of Wnt/β-catenin signaling by comparing skin and corneal development of Wnt/β-catenin gain of function (GOF) mutant mice. In the skin, Wnt/β-catenin signals have been suggested to play essential roles in regulating cell-cell interaction, cell proliferation and differentiation. Wnt signaling may be associated with basal cell carcinoma (BCC) of the skin. In the case of cornea, β-catenin GOF mutation leads to epithelial hyperplasia. Investigation of the mechanisms of growth factor signaling as a reference to general organogenesis could provide profound insights for understanding corneal development and pathogenesis. © 2012 Elsevier Inc. All rights reserved.

Myerson M.,Cardiovascular Disease Prevention Program | Myerson M.,Institute of Advanced Medicine | Poltavskiy E.,University of California at Davis | Armstrong E.J.,University of Colorado at Denver | And 3 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2014

Objective:: Patients with HIV may have an increased risk of cardiovascular disease (CVD). The objective of this study was to determine the prevalence, treatment, and control of low-density lipoprotein cholesterol (LDL-C) dyslipidemia and hypertension in a population of HIV-infected patients at an HIV/AIDS clinic in New York City. Methods:: Review of electronic medical records of 4278 HIV-infected patients aged 20 years or older in a racially and ethnically diverse urban HIV/AIDS clinic based in a large tertiary hospital and designated New York State AIDS Center that provides comprehensive care. LDL-C dyslipidemia was defined according to the National Cholesterol Education Program Adult Treatment Panel III goals and hypertension according to Joint National Committee VII criteria. Results:: The prevalence of LDL-C dyslipidemia was 35%. Ninety percent of patients with LDL-C dyslipidemia were treated and 75% of those treated were at goal. Patients in high-risk groups (56%), including known coronary heart disease (57%) or coronary heart disease equivalents (62%), were less likely to be at LDL-C goal. The prevalence of hypertension was 43%. Seventy-five percent of patients with hypertension were treated but only 57% overall were at goal. Conclusions:: Although most patients with HIV and LDL-C dyslipidemia or hypertension are treated, a significant percentage did not have adequate control of these risk factors. As patients with HIV are at higher risk for CVD and living to an age where CVD is more common, it will be important to identify ways to better manage and control CVD risk factors in this patient population. A comprehensive care model such as our setting may serve as an option. Copyright © 2014 by Lippincott Williams & Wilkins.

Sawada T.,Institute of Advanced Medicine | Arai D.,Institute of Advanced Medicine | Jing X.,Institute of Advanced Medicine | Furushima K.,Institute of Advanced Medicine | And 5 more authors.
PLoS ONE | Year: 2015

Ephs and FGFRs belong to a superfamily of receptor tyrosine kinases, playing important roles in stem cell biology. We previously reported that EphA4 and FGFR form a heterodimer following stimulation with ligands, trans-activating each other and signaling through a docking protein, FRS2α, that binds to both receptors. Here, we investigated whether the interaction between EphA4 and FGFRs can be generalized to other Ephs and FGFRs, and, in addition, examined the downstream signal mediating their function in embryonic neural stem/progenitor cells. We revealed that various Ephs and FGFRs interact with each other through similar molecular domains. When neural stem/progenitor cells were stimulated with FGF2 and ephrin-A1, the signal transduced from the EphA4/FGFR/FRS2α complex enhanced self-renewal, while stimulation with ephrin-A1 alone induced neuronal differentiation. The downstream signal required for neuronal differentiation appears to be MAP kinase mainly linked to the Ras family of G proteins. MAP kinase activation was delayed and sustained, distinct from the transient activation induced by FGF2. Interestingly, this effect on neuronal differentiation required the presence of FGFRs. Specific FGFR inhibitor almost completely abolished the function of ephrin-A1 stimulation. These findings suggest that the ternary complex of EphA, FGFR and FRS2α formed by ligand stimulation regulates self-renewal and differentiation of mouse embryonic neural stem/progenitor cells by ligand-specific fine tuning of the downstream signal via FRS2α. © 2015 Sawada et al.

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