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Coney Island, NY, United States

Wang J.C.,Brookdale University Hospital Medical Center | Kafeel M.I.,Brookdale University Hospital Medical Center | Avezbakiyev B.,Brookdale University Hospital Medical Center | Chen C.,Brookdale University Hospital Medical Center | And 6 more authors.

Background: Elevated histone deacetylase (HDAC) isoenzyme levels have been described in patients with carcinomas and leukemias. HDAC inhibitors (HDACi) have shown promise in the treatment of carcinomas and are currently under intense research. To make better use of HDACi in treating chronic lymphocytic leukemia (CLL), HDAC isoenzyme levels were studied. Methods: Quantitative reverse transcriptase polymerase chain reaction for HDAC isoenzyme was measured in 32 patients with CLL and compared with 17 normal volunteer controls. ZAP-70, CD38 and CD44 were also assayed and correlated to HDAC isoenzyme levels. Results: The results showed: (1) HDAC iso enzyme levels in CLL were significantly increased in class I including HDAC1 and HDAC3, in class II including HADC6, HDAC7, HDAC9 and HDAC10, and in class III including SIRT1 and SIRT6; (2) higher expression of HDAC isoenzyme levels was found in ZAP-70+ compared to ZAP-70-patients, and CD44 expression levels were correlated with HDAC isoenzyme expression levels in the majority of HDAC classes. Conclusions: These results suggest: (1) in CLL, elevated HDAC isoenzyme activity is not restricted to one class, and therefore, HDACi therapy may need to be directed to more than one specific class of HDAC; (2) higher HDAC expression activity may indicate a poor prognosis and more advanced disease stage (through indirect evidence), since higher values were found in patients with ZAP-70+ and higher CD44 expression levels. Copyright © 2012 S. Karger AG, Basel. Source

Brailoiu G.C.,Temple University | Gurzu B.,Temple University | Gao X.,Temple University | Parkesh R.,University of Oxford | And 8 more authors.
Journal of Biological Chemistry

Accumulating evidence implicates nicotinic acid adenine dinucleotide phosphate (NAADP) in the control of Ca2+-dependent functions. Little, however, is known concerning its role in the vascular endothelium, a major regulator of blood pressure. Here, we show that NAADP acetoxymethyl ester (NAADP-AM), a cell-permeant NAADP analog, increases cytosolic Ca2+ concentration in aortic endothelial cells. We demonstrate that these signals and those evoked by acetylcholine are blocked by disrupting acidic organelles with bafilomycin A1. In contrast, Ca2+ signals in response to thrombin are only partially inhibited by bafilomycin A1 treatment, and those to ATP were insensitive, suggesting that recruitment of acidic stores is agonist-specific. We further show that NAADP-evoked Ca2+ signals hyperpolarize endothelial cells and generate NO. Additionally, we demonstrate that NAADP dilates aortic rings in an endothelium- and NO-dependent manner. Finally, we show that intravenous administration of NAADP-AM into anesthetized rats decreases mean arterial pressure. Our data extend the actions of NAADP to the endothelium both in vitro and in vivo, pointing to a previously unrecognized role for this messenger in controlling blood pressure. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Source

A central problem of delusions is their imperviousness to counterargument. Although several existing theories account for aspects of delusional imperviousness, they omit the context of social interactions in which it occurs. Delusions elicit a specific and powerful social response from others: disbelief. Recent research has identified a backfire effect that happens when efforts to correct false beliefs strengthen, rather than weaken, conviction in those beliefs. It is proposed that delusional imperviousness is a special case of a backfire effect, in which repeated efforts to correct delusions paradoxically strengthen them. Delusions become impervious because they are strengthened by the counterarguments they elicit in others. © 2016 Informa UK Limited, trading as Taylor & Francis Group Source

Burton J.D.,Coney Island Hospital | Goldenberg D.M.,Garden State Cancer Center
Expert Opinion on Emerging Drugs

Importance of the field: B-cell non-Hodgkin lymphoma (NHL) is a significant public health problem as the most common hematologic malignancy in many areas of the world. Current treatments are generally effective, but only a minority of this large group of patients can be cured. Areas covered in this review: Progress in clinical development of novel, targeted agents and newer cytotoxic agents has led to improved, more durable responses in all major subtypes of NHL. This article covers novel therapeutic agents, which are investigational or registered recently for NHL and/or other cancers. Subtypes of B-cell NHL are addressed separately including relevant papers over the past 20 years. What the reader will gain: This review provides a better understanding of studies that have formed the basis for current treatment approaches for B-cell NHL. Also, areas of unmet need are covered. Novel agents are described along with their mechanisms of action, as well as how they might advance the treatment of B-cell NHL. Take home message: This review highlights advancements and the current state of knowledge by presenting clinical trial results as well as preclinical data and advances in prognostic and predictive factors that will pave the way to further progress in NHL. © 2010 Informa UK, Ltd. Source

Tsipursky M.S.,Retina Consultants | Tsipursky M.S.,University of Illinois at Urbana - Champaign | Heller M.A.,Coney Island Hospital | De Souza S.A.,Retina Consultants | And 4 more authors.

PURPOSE:: To evaluate the anatomical closure rate and visual outcome in patients undergoing pars plana vitrectomy with internal limiting membrane peeling without dye enhancement and with indocyanine green or triamcinolone acetonide assistance. METHODS:: This is a retrospective, comparative interventional case series. The electronic charts of 435 eyes of 415 patients with idiopathic macular holes who underwent macula hole surgery were reviewed from January 2003 to April 2010. The patients were assigned to 3 groups: no dye assistance (Group 1), indocyanine green-assisted (Group 2), and triamcinolone acetonide-assisted internal limiting membrane peel (Group 3). The data were recorded for 3-, 6-, and 12-month follow-up visits. Main outcome measures were postoperative visual acuity and macular hole closure. RESULTS:: The overall macular hole closure rate with a single surgery was 94.7% (108 of 114). In Group 1: 91.4% (191 of 209), in Group 2: 94.1% (112 of 119), and in Group 3: 95.9% (93 of 97) achieved closure. Closure rate for holes that were ≤400 μm in diameter was 98.8% compared with >400 μm, which was 90.4% (P = 0.001). There was a statistically significant (P < 0.001) improvement from preoperative visual acuity to postoperative visual acuity in all groups across all time points. There was no statistically significant visual acuity difference among three groups. At 12-month follow-up, 77.7% in Group 1, 66.1% in Group 2, and 81.3% in Group 3 achieved 20/50 visual acuity or better. CONCLUSION:: The study shows that good anatomical and functional results can be achieved with no dye and with indocyanine green or triamcinolone acetonide dye assistance for internal limiting membrane peeling during macular hole surgery. Overall, visual acuity levels did not differ among groups, although subanalysis of the results suggests subtle indocyanine green toxicity. © by Ophthalmic Communications Society, Inc. Source

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