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Pharmacological modulation of abnormal involuntary DOI-induced head twitch response movements in male DBA/2J mice: II. Effects of D3 dopamine receptor selective compounds

Latest UNTHSC Articles in Scopus - Fri, 03/27/2015 - 11:31pm
Author(s):Rangel-Barajas, C. | Malik, M. | Mach, R.H. | Luedtke, R.R.
Publication year: 2015
Journal / Book title: Neuropharmacology

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Clinical utility of sequential minimal residual disease measurements in the context of risk-based therapy in childhood acute lymphoblastic leukaemia: a prospective study.

Recent Research Articles from UNTHSC - Fri, 03/27/2015 - 3:29am

Clinical utility of sequential minimal residual disease measurements in the context of risk-based therapy in childhood acute lymphoblastic leukaemia: a prospective study.

Lancet Oncol. 2015 Mar 19;

Authors: Pui CH, Pei D, Coustan-Smith E, Jeha S, Cheng C, Bowman WP, Sandlund JT, Ribeiro RC, Rubnitz JE, Inaba H, Bhojwani D, Gruber TA, Leung WH, Downing JR, Evans WE, Relling MV, Campana D

Abstract
BACKGROUND: The level of minimal residual disease during remission induction is the most important prognostic indicator in patients with acute lymphoblastic leukaemia (ALL). We aimed to establish the clinical significance of minimal residual disease in a prospective trial that used sequential minimal residual disease measurements to guide treatment decisions.
METHODS: Between June 7, 2000, and Oct 24, 2007, 498 assessable patients with newly diagnosed ALL were enrolled in a clinical trial at St Jude Children's Research Hospital. We provisionally classified the risk of relapse as low, standard, or high according to patients' baseline clinical and laboratory features. Final risk assignment to establish treatment intensity was based mainly on minimal residual disease levels measured on days 19 and 46 of remission induction, and on week 7 of maintenance treatment. Additional measurements of minimal residual disease were made on weeks 17, 48, and 120 (end of treatment). The primary aim was to establish the association between event-free survival and patients' minimal residual disease levels during remission induction and sequentially post-remission. This trial was registered at ClinicalTrials.gov, number NCT00137111.
FINDINGS: Irrespective of the provisional risk classification, 10-year event-free survival was significantly worse for patients with 1% or greater minimal residual disease levels on day 19 compared with patients with lower minimal residual disease levels (69·2%, 95% CI 49·6-82·4, n=36 vs 95·5%, 91·7-97·5, n=244; p<0·001 for the provisional low-risk group and 65·1%, 50·7-76·2, n=56 vs 82·9%, 75·6-88·2, n=142; p=0·01 for the provisional standard-risk group). 12 patients with provisional low-risk ALL and 1% or higher minimal residual disease levels on day 19 but negative minimal residual disease (<0·01%) on day 46 were treated for standard-risk ALL and had a 10-year event-free survival of 88·9% (43·3-98·4). For the 280 provisional low-risk patients, a minimal residual disease level of less than 1% on day 19 predicted a better outcome, irrespective of the minimal residual disease level on day 46. Of provisional standard-risk patients with minimal residual disease of less than 1% on day 19, the 15 with persistent minimal residual disease on day 46 seemed to have an inferior 10-year event-free survival compared with the 126 with negative minimal residual disease (72·7%, 42·5-88·8 vs 84·0%, 76·3-89·4; p=0·06) after receiving the same post-remission treatment for standard-risk ALL. Of patients attaining negative minimal residual disease status after remission induction, minimal residual disease re-emerged in four of 382 studied on week 7, one of 448 at week 17, and one of 437 at week 48; all but one of these six patients died despite additional treatment. By contrast, relapse occurred in only two of the 11 patients who had decreasing minimal residual disease levels between the end of induction and week 7 of maintenance therapy and were treated with chemotherapy alone.
INTERPRETATION: Minimal residual disease levels during remission induction treatment have important prognostic and therapeutic implications even in the context of minimal residual disease-guided treatment. Sequential minimal residual disease monitoring after remission induction is warranted for patients with detectable minimal residual disease.
FUNDING: National Institutes of Health and American Lebanese Syrian Associated Charities.

PMID: 25800893 [PubMed - as supplied by publisher]

Downregulation of Aquaporin 4 Expression through Extracellular Signal-regulated Kinases1/2 Activation in Cultured Astrocytes Following Scratch-injury.

Recent Research Articles from UNTHSC - Fri, 03/27/2015 - 3:29am

Downregulation of Aquaporin 4 Expression through Extracellular Signal-regulated Kinases1/2 Activation in Cultured Astrocytes Following Scratch-injury.

Biomed Environ Sci. 2015 Mar;28(3):199-205

Authors: Shi ZF, Zhao WJ, Xu LX, Dong LP, Yang SH, Yuan F

Abstract
OBJECTIVE: To investigate the role of extracellular signal-regulated kinase1/2 (ERK1/2) pathway in the regulation of aquaporin 4 (AQP4) expression in cultured astrocytes after scratch-injury.
METHODS: The scratch-injury model was produced in cultured astrocytes of rat by a 10-μL plastic pipette tip. The morphological changes of astrocytes and lactate dehydrogenase (LDH) leakages were observed to assess the degree of scratch-injury. AQP4 expression was detected by immunofluorescence staining and Western blot, and phosphorylated-ERK1/2 (p-ERK1/2) expression was determined by Western blot. To explore the effect of ERK1/2 pathway on AQP4 expression in scratch-injured astrocytes, 10 µmol/L U0126 (ERK1/2 inhibitor) was incubated in the medium at 30 min before the scratch-injury in some groups.
RESULTS: Increases in LDH leakage were observed at 1, 12, and 24 h after scratch-injury, and AQP4 expression was reduced simultaneously. Decrease in AQP4 expression was associated with a significant increase in ERK1/2 activation. Furthermore, pretreatment with U0126 blocked both ERK1/2 activation and decrease in AQP4 expression induced by scratch-injury.
CONCLUSION: These results indicate that ERK1/2 pathway down-regulates AQP4 expression in scratch-injured astrocytes, and ERK1/2 pathway might be a novel therapeutic target in reversing the effects of astrocytes that contribute to traumatic brain edema.

PMID: 25800444 [PubMed - in process]

Chip-based nanoelectrospray ionization with Fourier transform mass spectrometric detection to screen for local anesthetics intended to mask limb sore in walking horses.

Recent Research Articles from UNTHSC - Fri, 03/27/2015 - 3:29am

Chip-based nanoelectrospray ionization with Fourier transform mass spectrometric detection to screen for local anesthetics intended to mask limb sore in walking horses.

J Mass Spectrom. 2015 Mar;50(3):533-7

Authors: Szarka S, Prokai L

Abstract
We report a high-throughput chip-based nanoelectrospray ionization method coupled with Fourier transform mass spectrometry to screen for local anesthetics in samples collected by swabbing. These drugs have been used to mask pain on the limbs of walking horses after forbidden practices of soring or physical abuse. Optimized for lidocaine, the method afforded sub-ppm mass accuracy for nine local anesthetics included in the study. From doped cotton swabs, two third and all of the analytes were detected after adding 10 ng and 100 ng of each drug, respectively. Benzocaine and/or lidocaine were found on positive swab samples collected during walking horse competitions. Copyright © 2015 John Wiley & Sons, Ltd.

PMID: 25800188 [PubMed - in process]

Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10.

Recent Research Articles from UNTHSC - Fri, 03/27/2015 - 3:29am
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Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10.

Eur J Immunol. 2015 Jan;45(1):180-91

Authors: Xie L, Choudhury GR, Winters A, Yang SH, Jin K

Abstract
Forkhead box P3 (Foxp3)(+) regulatory T (Treg) cells maintain the immune tolerance and prevent inflammatory responses in the periphery. However, the presence of Treg cells in the CNS under steady state has not been studied. Here, for the first time, we show a substantial TCRαβ (+) CD4(+) Foxp3(+) T-cell population (cerebral Treg cells) in the rat cerebrum, constituting more than 15% of the cerebral CD4(+) T-cell compartment. Cerebral Treg cells showed an activated/memory phenotype and expressed many Treg-cell signature genes at higher levels than peripheral Treg cells. Consistent with their activated/memory phenotype, cerebral Treg cells robustly restrained the LPS-induced inflammatory responses of brain microglia/macrophages, suggesting a role in maintaining the cerebral homeostasis by inhibiting the neuroinflammation. In addition, brain astrocytes were the helper cells that sustained Foxp3 expression in Treg cells through IL-2/STAT5 signaling, showing that the interaction between astrocytes and Treg cells contributes to the maintenance of Treg-cell identity in the brain. Taken together, our work represents the first study to characterize the phenotypic and functional features of Treg cells in the rat cerebrum. Our data have provided a novel insight for the contribution of Treg cells to the immunosurveillance and immunomodulation in the cerebrum under steady state.

PMID: 25329858 [PubMed - indexed for MEDLINE]

Neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma.

Recent Research Articles from UNTHSC - Fri, 03/27/2015 - 3:29am
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Neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma.

Invest Ophthalmol Vis Sci. 2015 Feb;56(2):893-907

Authors: Stankowska DL, Minton AZ, Rutledge MA, Mueller BH, Phatak NR, He S, Ma HY, Forster MJ, Yorio T, Krishnamoorthy RR

Abstract
PURPOSE: Glaucoma is an optic neuropathy commonly associated with elevated intraocular pressure (IOP), leading to optic nerve head (ONH) cupping, axon loss, and apoptosis of retinal ganglion cells (RGCs), which could ultimately result in blindness. Brn3b is a class-4 POU domain transcription factor that plays a key role in RGC development, axon outgrowth, and pathfinding. Previous studies suggest that a decrease in Brn3b levels occurs in animal models of glaucoma. The goal of this study was to determine if adeno-associated virus (AAV)-directed overexpression of the Brn3b protein could have neuroprotective effects following elevated IOP-mediated neurodegeneration.
METHODS: Intraocular pressure was elevated in one eye of Brown Norway rats (Rattus norvegicus), following which the IOP-elevated eyes were intravitreally injected with AAV constructs encoding either the GFP (rAAV-CMV-GFP and rAAV-hsyn-GFP) or Brn3b (rAAV-CMV-Brn3b and rAAV-hsyn-Brn3b). Retina sections through the ONH were stained for synaptic plasticity markers and neuroprotection was assessed by RGC counts and visual acuity tests.
RESULTS: Adeno-associated virus-mediated expression of the Brn3b protein in IOP-elevated rat eyes promoted an upregulation of growth associated protein-43 (GAP-43), actin binding LIM protein (abLIM) and acetylated α-tubulin (ac-Tuba) both posterior to the ONH and in RGCs. The RGC survival as well as axon integrity score were significantly improved in IOP-elevated rAAV-hsyn-Brn3b-injected rats compared with those of the IOP-elevated rAAV-hsyn-GFP- injected rats. Additionally, intravitreal rAAV-hsyn-Brn3b administration significantly restored the visual optomotor response in IOP-elevated rat eyes.
CONCLUSIONS: Adeno-associated virus-mediated Brn3b protein expression may be a suitable approach for promoting neuroprotection in animal models of glaucoma.

PMID: 25587060 [PubMed - indexed for MEDLINE]

Association of hypothyroidism with low-level arsenic exposure in rural West Texas

Latest UNTHSC Articles in Scopus - Thu, 03/26/2015 - 11:30pm
Author(s):Gong, G. | Basom, J. | Mattevada, S. | Onger, F.
Publication year: 2015
Journal / Book title: Environmental Research

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Cancer mortality in the meat and delicatessen departments of supermarkets (1950-2006)

Latest UNTHSC Articles in Scopus - Thu, 03/26/2015 - 11:30pm
Author(s):Johnson, E.S. | Cardarelli, K. | Jadhav, S. | Chedjieu, I.P. | Faramawi, M. | Fischbach, L. | Ndetan, H. | Wells, T.L.-C. | Patel, K.V. | Katyal, A.
Publication year: 2015
Journal / Book title: Environment International

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Arsenic exposure, hyperuricemia, and gout in US adults

Latest UNTHSC Articles in Scopus - Thu, 03/26/2015 - 11:30pm
Author(s):Kuo, C.-C. | Weaver, V. | Fadrowski, J.J. | Lin, Y.-S. | Guallar, E. | Navas-Acien, A.
Publication year: 2015
Journal / Book title: Environment International

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High therapeutic potential of positive allosteric modulation of α7 nAChRs in a rat model of traumatic brain injury: Proof-of-concept

Latest UNTHSC Articles in Scopus - Thu, 03/26/2015 - 11:30pm
Author(s):Gatson, J.W. | Simpkins, J.W. | Uteshev, V.V.
Publication year: 2015
Journal / Book title: Brain Research Bulletin

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AMPA receptor desensitization is the determinant of AMPA receptor mediated excitotoxicity in purified retinal ganglion cells

Latest UNTHSC Articles in Scopus - Thu, 03/26/2015 - 11:30pm
Author(s):Park, Y.H. | Mueller, B.H. | McGrady, N.R. | Ma, H.-Y. | Yorio, T.
Publication year: 2015
Journal / Book title: Experimental Eye Research

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Increased risk of genetic and epigenetic instability in human embryonic stem cells associated with specific culture conditions

Latest UNTHSC Articles in Scopus - Thu, 03/26/2015 - 11:30pm
Author(s):Garitaonandia, I. | Amir, H. | Boscolo, F.S. | Wambua, G.K. | Schultheisz, H.L. | Sabatini, K. | Morey, R. | Waltz, S. | Wang, Y.-C. | Tran, H. | Leonardo, T.R. | Nazor, K. | Slavin, I. | Lynch, C. | Li, Y. | Coleman, R. | Romero, I.G. | Altun, G. | Reynolds, D. | Dalton, S. | Parast, M. | Loring, J.F. | Laurent, L.C.
Publication year: 2015
Journal / Book title: PLoS ONE

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Development of biodegradable nanocarriers loaded with a monoclonal antibody

Latest UNTHSC Articles in Scopus - Thu, 03/26/2015 - 11:30pm
Author(s):Gdowski, A. | Ranjan, A. | Mukerjee, A. | Vishwanatha, J.
Publication year: 2015
Journal / Book title: International Journal of Molecular Sciences

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Synthesis, pharmacological evaluation and molecular modeling studies of triazole containing dopamine D3 receptor ligands

Latest UNTHSC Articles in Scopus - Thu, 03/26/2015 - 11:30pm
Author(s):Peng, X. | Wang, Q. | Mishra, Y. | Xu, J. | Reichert, D.E. | Malik, M. | Taylor, M. | Luedtke, R.R. | Mach, R.H.
Publication year: 2015
Journal / Book title: Bioorganic and Medicinal Chemistry Letters

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Neuroglobin Overexpression Inhibits AMPK Signaling and Promotes Cell Anabolism

Latest UNTHSC Articles in Scopus - Thu, 03/26/2015 - 11:30pm
Author(s):Cai, B. | Li, W. | Mao, X. | Winters, A. | Ryou, M.-G. | Liu, R. | Greenberg, D.A. | Wang, N. | Jin, K. | Yang, S.-H.
Publication year: 2015
Journal / Book title: Molecular Neurobiology

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Elephant (Elephas maximus) health and management in Asia: Variations in veterinary perspectives

Latest UNTHSC Articles in Scopus - Thu, 03/26/2015 - 11:30pm
Author(s):Miller, D. | Jackson, B. | Riddle, H.S. | Stremme, C. | Schmitt, D. | Miller, T.
Publication year: 2015
Journal / Book title: Veterinary Medicine International

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Underlying Data for Sequencing the Mitochondrial Genome with the Massively Parallel Sequencing Platform Ion Torrent™ PGM™

Latest UNTHSC Articles in Scopus - Thu, 03/26/2015 - 11:30pm
Author(s):Seo, S.B. | Zeng, X. | King, J.L. | Larue, B.L. | Assidi, M. | Al-Qahtani, M.H. | Sajantila, A. | Budowle, B.
Publication year: 2015
Journal / Book title: BMC Genomics

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Interaction between Nef and INI1/SMARCB1 augments replicability of HIV-1 in resting human peripheral blood mononuclear cells

Latest UNTHSC Articles in Scopus - Thu, 03/26/2015 - 11:30pm
Author(s):Pyeon, D. | Park, I.-W.
Publication year: 2015
Journal / Book title: Archives of Virology

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Rarity of the alzheimer disease-protective APP A673T variant in the United States

Latest UNTHSC Articles in Scopus - Thu, 03/26/2015 - 11:30pm
Author(s):Wang, L.-S. | Naj, A.C. | Graham, R.R. | Crane, P.K. | Kunkle, B.W. | Cruchaga, C. | Gonzalez Murcia, J.D. | Cannon-Albright, L. | Baldwin, C.T. | Zetterberg, H. | Blennow, K. | Kukull, W.A. | Faber, K.M. | Schupf, N. | Norton, M.C. | Tschanz, J.T. | Munger, R.G. | Corcoran, C.D. | Rogaeva, E. | Albert, M.S. | Albin, R.L. | Apostolova, L.G. | Arnold, S.E. | Barber, R. | Barmada, M.M. | Barnes, L.L. | Beach, T.G. | Becker, J.T. | Beecham, G.W. | Beekly, D. | Bennett, D.A. | Bigio, E.H. | Bird, T.D. | Blacker, D. | Boeve, B.F. | Bowen, J.D. | Boxer, A. | Burke, J.R. | Buxbaum, J.D. | Cairns, N.J. | Cao, C. | Carlson, C.S. | Carroll, S.L. | Chui, H.C. | Clark, D.G. | Cribbs, D.H. | Crocco, E.A. | DeCarli, C. | DeKosky, S.T. | Demirci, F.Y. | Dick, M. | Dickson, D.W. | Duara, R. | Ertekin-Taner, N. | Fallon, K.B. | Farlow, M.R. | Ferris, S. | Frosch, M.P. | Galasko, D.R. | Ganguli, M. | Gearing, M. | Geschwind, D.H. | Ghetti, B. | Gilbert, J.R. | Glass, J.D. | Graff-Radford, N.R. | Growdon, J.H. | Hamilton, R.L. | Hamilton-Nelson, K.L. | Harrell, L.E. | Head, E. | Honig, L.S. | Hulette, C.M. | Hyman, B.T. | Jarvik, G.P. | Jicha, G.A. | Jin, L.-W. | Jun, G. | Kamboh, M.I. | Karydas, A. | Kaye, J.A. | Kim, R. | Koo, E.H. | Kowall, N.W. | Kramer, J.H. | Kramer, P. | LaFerla, F.M. | Lah, J.J. | Leverenz, J.B. | Levey, A.I. | Li, G. | Lieberman, A.P. | Lopez, O.L. | Lunetta, K.L. | Lyketsos, C.G. | Mack, W.J. | Marson, D.C. | Martin, E.R. | Martiniuk, F. | Mash, D.C. | Masliah, E. | McCormick, W.C. | McCurry, S.M. | McDavid, A.N. | McKee, A.C. | Mesulam, M.M. | Miller, B.L. | Miller, C.A. | Miller, J.W. | Montine, T.J. | Morris, J.C. | Murrell, J.R. | Olichney, J.M. | Parisi, J.E. | Perry, W. | Peskind, E. | Petersen, R.C. | Pierce, A. | Poon, W.W. | Potter, H. | Quinn, J.F. | Raj, A. | Raskind, M. | Reiman, E.M. | Reisberg, B. | Reitz, C. | Ringman, J.M. | Roberson, E.D. | Rosen, H.J. | Rosenberg, R.N. | Sano, M. | Saykin, A.J. | Schneider, J.A. | Schneider, L.S. | Seeley, W.W. | Smith, A.G. | Sonnen, J.A. | Spina, S. | Stern, R.A. | Tanzi, R.E. | Thornton-Wells, T.A. | Trojanowski, J.Q. | Troncoso, J.C. | Tsuang, D.W. | Van Deerlin, V.M. | Van Eldik, L.J. | Vardarajan, B.N. | Vinters, H.V. | Vonsattel, J.P. | Weintraub, S. | Welsh-Bohmer, K.A. | Williamson, J. | Wishnek, S. | Woltjer, R.L. | Wright, C.B. | Younkin, S.G. | Yu, C.-E. | Yu, L. | Lin, C.-F. | Dombroski, B.A. | Cantwell, L.B. | Partch, A. | Valladares, O. | Hakonarson, H. | St George-Hyslop, P. | Green, R.C. | Goate, A.M. | Foroud, T.M. | Carney, R.M. | Larson, E.B. | Behrens, T.W. | Kauwe, J.S.K. | Haines, J.L. | Farrer, L.A. | Pericak-Vance, M.A. | Mayeux, R. | Schellenberg, G.D.
Publication year: 2015
Journal / Book title: JAMA Neurology

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Treatment for preventing tuberculosis in children and adolescents: A randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and Isoniazid

Latest UNTHSC Articles in Scopus - Thu, 03/26/2015 - 11:30pm
Author(s):Villarino, M.E. | Scott, N.A. | Weis, S.E. | Weiner, M. | Conde, M.B. | Jones, B. | Nachman, S. | Oliveira, R. | Moro, R.N. | Shang, N. | Goldberg, S.V. | Sterling, T.R.
Publication year: 2015
Journal / Book title: JAMA Pediatrics

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