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Tara L Moore, Monica A Pessina, Seth P Finklestein, Ronald J Killiany, Bethany Bowley, Larry Benowitz, Douglas L Rosene
BACKGROUND: Inosine, a naturally occurring purine nucleoside, has been shown to stimulate axonal growth in cell culture and promote corticospinal tract axons to sprout collateral branches after stroke, spinal cord injury and TBI in rodent models. OBJECTIVE: To explore the effects of inosine on the recovery of motor function following cortical injury in the rhesus monkey. METHODS: After being trained on a test of fine motor function of the hand, monkeys received a lesion limited to the area of the hand representation in primary motor cortex...
September 21, 2016: Restorative Neurology and Neuroscience
David T Teachey, Simon F Lacey, Pamela A Shaw, J Joseph Melenhorst, Shannon L Maude, Noelle Frey, Edward Pequignot, Vanessa E Gonzalez, Fang Chen, Jeffrey Finklestein, David M Barrett, Scott L Weiss, Julie C Fitzgerald, Robert A Berg, Richard Aplenc, Colleen Callahan, Susan R Rheingold, Zhaohui Zheng, Stefan Rose-John, Jason C White, Farzana Nazimuddin, Gerald Wertheim, Bruce L Levine, Carl H June, David L Porter, Stephan A Grupp
UNLABELLED: Chimeric antigen receptor (CAR)-modified T cells with anti-CD19 specificity are a highly effective novel immune therapy for relapsed/refractory acute lymphoblastic leukemia. Cytokine release syndrome (CRS) is the most significant and life-threatening toxicity. To improve understanding of CRS, we measured cytokines and clinical biomarkers in 51 CTL019-treated patients. Peak levels of 24 cytokines, including IFNγ, IL6, sgp130, and sIL6R, in the first month after infusion were highly associated with severe CRS...
June 2016: Cancer Discovery
Jennifer F Iaci, Tom J Parry, Zhihong Huang, Elias Pavlopoulos, Seth P Finklestein, Jingmei Ren, Anthony Caggiano
Cimaglermin (neuregulin 1β3, glial growth factor 2) is a neuregulin growth factor family member in clinical development for chronic heart failure. Previously, in a permanent middle cerebral artery occlusion (pMCAO) rat stroke model, systemic cimaglermin treatment initiated up to 7 days after ischemia onset promoted recovery without reduced lesion volume. Presented here to extend the evidence are two studies that use a rat stroke model to evaluate the effects of cimaglermin dose level and dose frequency initiated 24 hr after pMCAO...
March 2016: Journal of Neuroscience Research
Aaron P Rapoport, Edward A Stadtmauer, Gwendolyn K Binder-Scholl, Olga Goloubeva, Dan T Vogl, Simon F Lacey, Ashraf Z Badros, Alfred Garfall, Brendan Weiss, Jeffrey Finklestein, Irina Kulikovskaya, Sanjoy K Sinha, Shari Kronsberg, Minnal Gupta, Sarah Bond, Luca Melchiori, Joanna E Brewer, Alan D Bennett, Andrew B Gerry, Nicholas J Pumphrey, Daniel Williams, Helen K Tayton-Martin, Lilliam Ribeiro, Tom Holdich, Saul Yanovich, Nancy Hardy, Jean Yared, Naseem Kerr, Sunita Philip, Sandra Westphal, Don L Siegel, Bruce L Levine, Bent K Jakobsen, Michael Kalos, Carl H June
Despite recent therapeutic advances, multiple myeloma (MM) remains largely incurable. Here we report results of a phase I/II trial to evaluate the safety and activity of autologous T cells engineered to express an affinity-enhanced T cell receptor (TCR) recognizing a naturally processed peptide shared by the cancer-testis antigens NY-ESO-1 and LAGE-1. Twenty patients with antigen-positive MM received an average 2.4 × 10(9) engineered T cells 2 d after autologous stem cell transplant. Infusions were well tolerated without clinically apparent cytokine-release syndrome, despite high IL-6 levels...
August 2015: Nature Medicine
Praveen Kulkarni, William Kenkel, Seth P Finklestein, Thomas M Barchet, JingMei Ren, Mathew Davenport, Martha E Shenton, Zora Kikinis, Mark Nedelman, Craig F Ferris
Traumatic brain injury (TBI) can occur anywhere along the cortical mantel. While the cortical contusions may be random and disparate in their locations, the clinical outcomes are often similar and difficult to explain. Thus a question that arises is, do concussions at different sites on the cortex affect similar subcortical brain regions? To address this question we used a fluid percussion model to concuss the right caudal or rostral cortices in rats. Five days later, diffusion tensor MRI data were acquired for indices of anisotropy (IA) for use in a novel method of analysis to detect changes in gray matter microarchitecture...
2015: PloS One
Moose Finklestein
No abstract text is available yet for this article.
2014: Narrative Inquiry in Bioethics
Jeannie S Huang, Lindsay Dillon, Laura Terrones, Lynn Schubert, William Roberts, Jerry Finklestein, Maria C Swartz, Gregory J Norman, Kevin Patrick
BACKGROUND: Children surviving acute lymphoblastic leukemia (ALL) are at increased risk for overweight and obesity over that of the general population. Whether a generic or tailored approach to weight management is needed for cancer survivors has yet to be tested. PROCEDURE: Thirty-eight youth 8-18 years with BMI ≥ 85% who had survived ALL were recruited for a randomized clinical trial evaluating a weight management intervention (WMI) tailored for childhood ALL survivors (Fit4Life)...
May 2014: Pediatric Blood & Cancer
Tara L Moore, Monica A Pessina, Seth P Finklestein, Brian C Kramer, Ronald J Killiany, Douglas L Rosene
We investigated the efficacy on recovery of function following controlled cortical ischemia in the monkey of the investigational cell drug product, CNTO 0007. This drug contains a cellular component, human umbilical tissue-derived cells, in a proprietary thaw and inject formulation. Results demonstrate significantly better recovery of motor function in the treatment group with no difference between groups in the volume or surface area of ischemic damage, suggesting that the cells stimulated plasticity.
December 2013: Somatosensory & Motor Research
Jennifer F Iaci, Tom J Parry, Zhihong Huang, Seth P Finklestein, Jingmei Ren, Dana K Barrile, Matthew D Davenport, Rui Wu, Andrew R Blight, Anthony O Caggiano
BACKGROUND AND PURPOSE: Stroke survivors often have permanent deficits that are only partially addressed by physical therapy. This study evaluated the effects of dalfampridine, a potassium channel blocker, on persistent sensorimotor deficits in rats with treatment initiated 4 or 8 weeks after stroke. METHODS: Rats underwent permanent middle cerebral artery occlusion. Sensorimotor function was measured using limb-placing and body-swing symmetry tests, which normally show a partial recovery from initial deficits that plateaus ≈4 weeks after permanent middle cerebral artery occlusion...
July 2013: Stroke; a Journal of Cerebral Circulation
Etan Orgel, Laura Zung, Lingyun Ji, Jerry Finklestein, James Feusner, David R Freyer
BACKGROUND: Anthracycline agents are used for treatment of acute myeloid leukemia (AML) but may cause late-onset cardiomyopathy. Current frontline therapy for AML in North America, as reflected in the approach of the Children's Oncology Group (COG) and other pediatric consortia, is adapted from the anthracyline-intensive Medical Research Council (MRC) regimen. The purpose of this study was to describe early post-treatment cardiac function as a potential indicator of acute and long-term risk associated with this approach...
September 2013: Pediatric Blood & Cancer
Alex R Hastie, Lingli Dong, Alexis Smith, Jeff Finklestein, Ernest T Lam, Naxin Huo, Han Cao, Pui-Yan Kwok, Karin R Deal, Jan Dvorak, Ming-Cheng Luo, Yong Gu, Ming Xiao
Next-generation sequencing (NGS) technologies have enabled high-throughput and low-cost generation of sequence data; however, de novo genome assembly remains a great challenge, particularly for large genomes. NGS short reads are often insufficient to create large contigs that span repeat sequences and to facilitate unambiguous assembly. Plant genomes are notorious for containing high quantities of repetitive elements, which combined with huge genome sizes, makes accurate assembly of these large and complex genomes intractable thus far...
2013: PloS One
Michal Finklestein, Avital Laufer, Zahava Solomon
UNLABELLED: The aim of this study was to examine the relations between coping strategies, posttraumatic stress disorder (PTSD), and dissociation among Jewish Ethiopian refugees in Israel (following exposure to pre-, peri- and post-migration stressful events). METHOD: A random sample (N = 478) of three waves of refugees took part in the research (N = 165; N = 169; N = 144). Religiosity, coping strategies, stressful and traumatic events, pre- and peri- migration, post-migration difficulties, posttraumatic symptoms, and dissociation were assessed...
December 2012: Scandinavian Journal of Psychology
Frank S Menniti, Jingmei Ren, Dana K Sietsma, Angel Som, Fredrick R Nelson, Diane T Stephenson, Barbara A Tate, Seth P Finklestein
PURPOSE: Phosphodiesterase 5A (PDE5A) inhibitors improve functional recovery in experimental models of stroke in rats when treatment is delayed and without effect on infarct volume. PDE5A is expressed to only a very limited extent in forebrain tissues, raising the possibility that the locus of effect for the inhibitors is outside the brain. To start to address this question, we determined whether PDE5A inhibitors must have the ability to cross the blood brain barrier to improve recovery...
2012: Restorative Neurology and Neuroscience
Sarit Bar-Sheshet Itach, Maya Finklestein, Nir Etkovitz, Haim Breitbart
In order to fertilize the oocyte, sperm must undergo a series of biochemical changes in the female reproductive tract, known as capacitation. Once capacitated, spermatozoon can bind to the zona pellucida of the egg and undergo the acrosome reaction (AR), a process that enables its penetration and fertilization of the oocyte. Important processes that characterize sperm capacitation are actin polymerization and the development of hyper-activated motility (HAM). Previously, we showed that Phospholipase D (PLD)-dependent actin polymerization occurs during sperm capacitation, however the role of this process in sperm capacitation is not yet known...
February 15, 2012: Developmental Biology
S P Finklestein, P J Fanning, C G Caday, P P Powell, J Foster, E M Clifford, M Klagsbrun
Focal injury to the mammalian central nervous system (CNS) results in a cascade of cellular responses - including glial and capillary proliferation and neural sprouting - that contribute to the repair of neural tissue and to the recovery of neurological function. Fibroblast growth factors (FGFs) are heparin-binding polypeptides with potent trophic effects on CNS glia, endothelia, and neurons; both acidic and basic forms are found in the mammalian CNS. We used heparin-affinity chromatography coupled to Balb/c 3T3 mitogenic assay to show a marked increase in levels of bioactive FGFs in tissue surrounding focal cortical lesions of the mature rat brain at one week after injury...
January 1, 1990: Restorative Neurology and Neuroscience
Tara L Moore, Ronald J Killiany, Monica A Pessina, Mark B Moss, Seth P Finklestein, Douglas L Rosene
Studies of recovery from stroke mainly utilize rodent models and focus primarily on young subjects despite the increased prevalence of stroke with age and the fact that recovery of function is more limited in the aged brain. In the present study, a nonhuman primate model of cortical ischemia was developed to allow the comparison of impairments in young and middle-aged monkeys. Animals were pretrained on a fine motor task of the hand and digits and then underwent a surgical procedure to map and lesion the hand-digit representation in the dominant motor cortex...
March 2012: Neurobiology of Aging
W M Kazmierski, P C Fritch
This chapter describes the synthetic procedures leading to ether dipeptide isosteres of the Phe-ψ[CH(2)O]-spiro-C(x) (9a-9e, Fig. 1) and Phe-ψ[CH(2)O]-Allylglycine (13, Fig. 2). Development of methods which lead to mimetics of amide bonds is central to the conversion of peptide leads into pharmaceutically viable molecules. Our strategy utilizes template 1, which provides derivatives 6b-6e upon alkylation with I, Cl-alkanes (C(3)-C(6)). Subsequent Finklestein conversion to iodides 7b-7e is then followed by cyclization to spirocyclic derivatives 5b-5e (Fig...
1999: Methods in Molecular Medicine
Charlotte M Niemeyer, Michelle W Kang, Danielle H Shin, Ingrid Furlan, Miriam Erlacher, Nancy J Bunin, Severa Bunda, Jerry Z Finklestein, Kathleen M Sakamoto, Thomas A Gorr, Parinda Mehta, Irene Schmid, Gabriele Kropshofer, Selim Corbacioglu, Peter J Lang, Christoph Klein, Paul-Gerhard Schlegel, Andrea Heinzmann, Michaela Schneider, Jan Starý, Marry M van den Heuvel-Eibrink, Henrik Hasle, Franco Locatelli, Debbie Sakai, Sophie Archambeault, Leslie Chen, Ryan C Russell, Stephanie S Sybingco, Michael Ohh, Benjamin S Braun, Christian Flotho, Mignon L Loh
CBL encodes a member of the Cbl family of proteins, which functions as an E3 ubiquitin ligase. We describe a dominant developmental disorder resulting from germline missense CBL mutations, which is characterized by impaired growth, developmental delay, cryptorchidism and a predisposition to juvenile myelomonocytic leukemia (JMML). Some individuals experienced spontaneous regression of their JMML but developed vasculitis later in life. Importantly, JMML specimens from affected children show loss of the normal CBL allele through acquired isodisomy...
September 2010: Nature Genetics
Jennifer F Iaci, Anindita Ganguly, Seth P Finklestein, Tom J Parry, Jingmei Ren, Subhash Saha, Dana K Sietsma, Maya Srinivas, Andrea M Vecchione, Anthony O Caggiano
Neuregulins are a family of growth factors essential for normal cardiac and nervous system development. The EGF-like domain of neuregulins contains the active site which binds and activates signaling cascades through ErbB receptors. A neuregulin-1 gene EGF-like fragment demonstrated neuroprotection in the transient middle cerebral artery occlusion (MCAO) stroke model and drastically reduced infarct volume (Xu et al., 2004). Here we use a permanent MCAO rat model to initially compare two products of the neuregulin-1 gene and also assess levels of recovery with acute versus delayed time to treatment...
December 2010: Neuropharmacology
Vladimir Hachinski, Geoffrey A Donnan, Philip B Gorelick, Werner Hacke, Steven C Cramer, Markku Kaste, Marc Fisher, Michael Brainin, Alastair M Buchan, Eng H Lo, Brett E Skolnick, Karen L Furie, Graeme J Hankey, Miia Kivipelto, John Morris, Peter M Rothwell, Ralph L Sacco, Sidney C Smith, Yulun Wang, Alan Bryer, Gary A Ford, Costantino Iadecola, Sheila C O Martins, Jeff Saver, Veronika Skvortsova, Mark Bayley, Martin M Bednar, Pamela Duncan, Lori Enney, Seth Finklestein, Theresa A Jones, Lalit Kalra, Jeff Kleim, Ralph Nitkin, Robert Teasell, Cornelius Weiller, Bhupat Desai, Mark P Goldberg, Wolf-Dieter Heiss, Osmo Saarelma, Lee H Schwamm, Yukito Shinohara, Bhargava Trivedi, Nils Wahlgren, Lawrence K Wong, Antoine Hakim, Bo Norrving, Stephen Prudhomme, Natan M Bornstein, Stephen M Davis, Larry B Goldstein, Didier Leys, Jaakko Tuomilehto
BACKGROUND AND PURPOSE: The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. METHODS: Preliminary work was performed by seven working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. RESULTS: Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science...
August 2010: International Journal of Stroke: Official Journal of the International Stroke Society
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