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https://www.readbyqxmd.com/read/28079862/extra-neuronal-pathology-in-a-canine-model-of-cln2-neuronal-ceroid-lipofuscinosis-after-intracerebroventricular-gene-therapy-that-delays-neurological-disease-progression
#1
M L Katz, G C Johnson, S B Leach, B G Williamson, J R Coates, R E H Whiting, D P Vansteenkiste, M S Whitney
CLN2 neuronal ceroid lipofuscinosis is a hereditary lysosomal storage disease with primarily neurological signs that results from mutations in TPP1 which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Studies using a canine model for this disorder demonstrated that delivery of TPP1 enzyme to the cerebrospinal fluid (CSF) by intracerebroventricular administration of an AAV-TPP1 vector resulted in substantial delays in the onset and progression of neurological signs and prolongation of lifespan...
January 12, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28079061/progressive-decline-in-hippocampal-ca1-volume-in-individuals-at-ultra-high-risk-for-psychosis-who-do-not-remit-findings-from-the-longitudinal-youth-at-risk-study
#2
New Fei Ho, Daphne J Holt, Mike Cheung, Juan Eugenio Iglesias, Alex Goh, Mingyuan Wang, Joseph Kw Lim, Joshua de Souza, Joann S Poh, Yuen Mei See, Alison R Adcock, Stephen J Wood, Michael Wl Chee, Jimmy Lee, Juan Zhou
Most individuals identified as ultra high-risk for psychosis (UHR) do not develop frank psychosis. They continue to exhibit subthreshold symptoms, or go on to fully remit. Prior work has shown that the volume of CA1, a subfield of the hippocampus, is selectively reduced in the early stages of schizophrenia. Here, we aimed to determine whether patterns of volume change of CA1 are different in UHR individuals who do or do not achieve symptomatic remission. Structural MRI scans were acquired at baseline and at 1-2 follow-up time points (at 12-month intervals) from 147 UHR and healthy control subjects...
January 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28079060/intranasal-lactoferrin-enhances-%C3%AE-secretase-dependent-amyloid-precursor-protein-processing-via-the-erk1-2-creb-and-hif-1%C3%AE-pathways-in-an-alzheimer-s-disease-mouse-model
#3
Chuang Guo, Zhao-Hui Yang, Shuai Zhang, Rui Chai, Han Xue, Yan-Hui Zhang, Jia-Yi Li, Zhan-You Wang
Growing evidence suggests that lactoferrin (Lf), an iron-binding glycoprotein, is a pleiotropic functional nutrient. Additionally, Lf was recently implicated as a neuroprotective agent. These properties make Lf a valuable therapeutic candidate for the treatment of Alzheimer's disease (AD). However, the mechanisms regulating the physiological roles of Lf in the pathologic condition of AD remain unknown. In the present study, an APPswe/PS1DE9 transgenic mouse model of AD was used. We explored whether intranasal human Lf (hLf) administration could reduce β-amyloid (Aβ) deposition and ameliorate cognitive decline in this AD model...
January 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28079059/co-variation-of-peripheral-levels-of-mir-1202-and-brain-activity-and-connectivity-during-antidepressant-treatment
#4
Juan Pablo Lopez, Fabricio Pereira, Stéphane Richard-Devantoy, Marcelo Berlim, Eduardo Chachamovich, Laura M Fiori, Paola Niola, Gustavo Turecki, Fabrice Jollant
MicroRNAs are short non-coding molecules that play a major role in regulating gene expression. Peripheral levels of miR-1202 have been shown to predict and mediate antidepressant response. However, it is not clear to what extent these peripheral measures reflect central neural changes in vivo. We approached this problem with the combined use of peripheral miR-1202 measures and neuroimaging. At baseline and after 8 weeks of Desvenlafaxine (50-100 mg die), twenty patients were scanned with 3T Magnetic Resonance Imaging, first at rest then during the Go/NoGo task, a classical test of response inhibition...
January 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28077863/what-have-human-experimental-overfeeding-studies-taught-us-about-adipose-tissue-expansion-and-susceptibility-to-obesity-and-metabolic-complications
#5
REVIEW
D J Cuthbertson, T Steele, J P Wilding, J C G Halford, J A Harrold, M Hamer, F Karpe
Overfeeding experiments, in which we impose short-term positive energy balance, help unravel the cellular, physiological and behavioural adaptations to nutrient excess. These studies mimic longer-term mismatched energy expenditure and intake. There is considerable inter-individual heterogeneity in the magnitude of weight gain when exposed to similar relative caloric excess reflecting variable activation of compensatory adaptive mechanisms. Significantly, given similar relative weight gain, individuals may be protected from/predisposed to metabolic complications (insulin resistance, dyslipidaemia, hypertension), non-alcoholic fatty liver disease and cardiovascular disease...
January 12, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28077862/what-are-the-challenges-in-developing-effective-health-policies-for-obesity
#6
REVIEW
M Binks, S-H Chin
Identifying and implementing thoughtful, evidence based (or at least evidence informed) public health approaches to impacting obesity is a complex issue fraught with multiple challenges. These challenges begin with determining whether obesity policy approaches should be implemented. This is considered within the broader context of how common public health policy approaches may be relevant and applied to obesity. Additional challenges discussed include inconsistencies in clearly identifying obesity policy targets (e...
January 12, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28077861/economics-and-obesity-policy
#7
REVIEW
J L Lusk
This paper elucidates the challenges surrounding the economics of some popular obesity-related policy proposals. Solid economic justifications for anti-obesity policies are often lacking, and pragmatically evidence suggests policies like fat and soda taxes or restrictions on food stamp spending are unlikely to substantively affect obesity prevalence. In short, many of the same factors that make obesity such a complicated and multifaceted issue extend to the economic analysis public health policies.International Journal of Obesity accepted article preview online, 12 January 2017...
January 12, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28075429/telomerase-specific-oncolytic-adenovirus-expressing-trail-suppresses-peritoneal-dissemination-of-gastric-cancer
#8
W Zhou, S Dai, H Zhu, Z Song, Z Han, Y Cai, J B Lee, Z Li, X Hu, B Fang, C He, X Huang
Peritoneal dissemination is the most common condition of metastasis in gastric cancer. The survival duration of a patient with advanced stage gastric cancer, may be improved by gene therapy. In this study, we used an oncolytic adenovirus vector (Ad/TRAIL-E1) that expresses both the TRAIL and E1A genes under the control of a tumor-specific promoter. We evaluated the anti-tumor effect of Ad/TRAIL-E1 on gastric cancer cells in vitro, as well as in vivo in a xenograft peritoneal carcinomatosis mouse model. Our data showed that Ad/TRAIL-E1 induced TRAIL-mediated apoptosis in gastric cancer cell lines, but not in the normal cell lines...
January 11, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28075428/balanced-secretion-of-anti-cea-x-anti-cd3-diabody-chains-using-the-2a-self-cleaving-peptide-maximizes-diabody-assembly-and-tumor-specific-cytotoxicity
#9
K Mølgaard, M Compte, N Nuñez-Prado, S L Harwood, L Sanz, L Alvarez-Vallina
Adoptive transfer of genetically engineered human cells secreting bispecific T cell engagers has shown encouraging therapeutic effects in preclinical models of cancer. However, reducing the toxicity and improving the effectiveness of this emerging immunotherapeutic strategy will be critical to its successful application. We have demonstrated that for gene-based bispecific antibody strategies, two-chain diabodies have a better safety profile than single-chain tandem scFvs, because their reduced tendency to form aggregates reduces the risk of inducing antigen-independent T cell activation...
January 11, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28074831/rgs9-2-modulates-responses-to-oxycodone-in-pain-free-and-chronic-pain-states
#10
Sevasti Gaspari, Valeria Cogliani, Lefteris Manouras, Ethan M Anderson, Vasiliki Mitsi, Kleopatra Avrampou, Fiona B Carr, Venetia Zachariou
Regulator of G protein signalling 9-2 (RGS9-2) is a striatal enriched signal transduction modulator, known to play a critical role in the development of addiction-related behaviours following exposure to psychostimulants or opioids. RGS9-2 controls the function of several GPCRs, including dopamine and mu opioid (MOR) receptors. We previously showed that RGS9-2 complexes negatively control morphine analgesia, and promote the development of morphine tolerance. In contrast, RGS9-2 positively modulates the actions of other opioid analgesics, such as fentanyl and methadone...
January 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28074830/tet1-in-nucleus-accumbens-opposes-depression-and-anxiety-like-behaviors
#11
Jian Feng, Catherine J Pena, Immanuel Purushothaman, Olivia Engmann, Deena Walker, Amber N Brown, Orna Issler, Marie Doyle, Eileen Harrigan, Ezekiell Mouzon, Vincent Vialou, Li Shen, Meelad M Dawlaty, Rudolf Jaenisch, Eric J Nestler
Depression is a leading cause of disease burden, yet current therapies fully treat <50% of affected individuals. Increasing evidence implicates epigenetic mechanisms in depression and antidepressant action. Here, we examined a possible role for the DNA dioxygenase, ten eleven translocation protein 1 (TET1), in depression-related behavioral abnormalities. We applied chronic social defeat stress, an ethologically validated mouse model of depression-like behaviors, and examined Tet1 expression changes in nucleus accumbens (NAc), a key brain reward region...
January 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28074072/targeting-bet-proteins-improves-the-therapeutic-efficacy-of-bcl-2-inhibition-in-t-cell-acute-lymphoblastic-leukemia
#12
S Peirs, V Frismantas, F Matthijssens, W Van Loocke, T Pieters, N Vandamme, B Lintermans, M P Dobay, G Berx, B Poppe, S Goossens, B C Bornhauser, J-P Bourquin, P Van Vlierberghe
Inhibition of anti-apoptotic BCL-2 has recently emerged as a promising new therapeutic strategy for the treatment of a variety of human cancers, including leukemia. Here, we used T-cell acute lymphoblastic leukemia as a model system to identify novel synergistic drug combinations with the BH3 mimetic venetoclax (ABT-199). In vitro drug screening in primary leukemia specimens that were derived from patients with high risk of relapse or relapse and cell lines revealed synergistic activity between venetoclax and the BET bromodomain inhibitor JQ1...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074071/olaptesed-pegol-an-anti-cxcl12-sdf-1-spiegelmer-%C3%A2-alone-and-with-bortezomib-dexamethasone-in-relapsed-refractory-multiple-myeloma-a-phase-iia-study
#13
H Ludwig, K Weisel, M T Petrucci, X Leleu, A M Cafro, L Garderet, C Leitgeb, R Foa, R Greil, I Yakoub-Agha, D Zboralski, S Vauléon, T Dümmler, D Beyer, Ana Kruschinski, K Riecke, M Baumann, M Engelhardt
Leukemia accepted article preview online, 11 January 2017. doi:10.1038/leu.2017.5.
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074070/gain-of-function-in-jak2-v617f-positive-t-cells
#14
G Nishanth, D Wolleschak, C Fahldieck, T Fischer, A Mullally, F Perner, T M Schnöder, S Just, F H Heidel, D Schlüter
Leukemia accepted article preview online, 11 January 2017. doi:10.1038/leu.2017.6.
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074069/myelodysplastic-syndromes-and-bone-loss-in-mice-and-men
#15
H Weidner, M Rauner, F Trautmann, J Schmitt, E Balaian, A Mies, S Helas, U Baschant, C Khandanpour, M Bornhäuser, L C Hofbauer, U Platzbecker
Leukemia accepted article preview online, 11 January 2017. doi:10.1038/leu.2017.7.
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074068/a-cpg-island-methylator-phenotype-in-acute-myeloid-leukemia-independent-of-idh-mutations-and-associated-with-a-favorable-outcome
#16
A D Kelly, H Kroeger, J Yamazaki, R Taby, F Neumann, S Yu, J T Lee, B Patel, Y Li, R He, S Liang, Y Lu, M Cesaroni, S A Pierce, S M Kornblau, C E Bueso-Ramos, F Ravandi, H M Kantarjian, J Jelinek, J-Pj Issa
Genetic changes are infrequent in acute myeloid leukemia (AML) compared to other malignancies and often involve epigenetic regulators, suggesting that an altered epigenome may underlie AML biology and outcomes. In 96 AML cases including 65 pilot samples selected for cured/not-cured, we found higher CpG island (CGI) promoter methylation in cured patients. Expanded genome-wide digital restriction enzyme analysis of methylation (DREAM) data revealed a CGI methylator phenotype independent of IDH1/2 mutations we term AML-CIMP (A-CIMP(+))...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074067/expression-of-the-ctla-4-ligand-cd86-on-plasmacytoid-dendritic-cells-pdc-predicts-risk-of-disease-recurrence-after-treatment-discontinuation-in-cml
#17
C Schütz, S Inselmann, S Sausslele, C T Dietz, M C Müller, E Eigendorff, C A Brendel, S K Metzelder, T H Brümmendorf, C Waller, J Dengler, M E Goebeler, R Herbst, G Freunek, S Hanzel, T Illmer, Y Wang, T Lange, F Finkernagel, R Hehlmann, M Huber, A Neubauer, A Hochhaus, J Guilhot, F X Mahon, M Pfirrmann, A Burchert
It is unknown, why only a minority of chronic myeloid leukemia (CML) patients sustains treatment free remission (TFR) after discontinuation of tyrosine kinase inhibitor (TKI) therapy in deep molecular remission (MR). Here we studied, whether expression of the T-cell inhibitory receptor (CTLA-4)-ligand CD86 (B7.2) on plasmacytoid dendritic cells (pDC) affects relapse risk after TKI cessation. CML patients in MR displayed significantly higher CD86(+)pDC frequencies than normal donors (P<0·0024), whereas TFR patients had consistently low CD86(+)pDC (n=12)...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074066/preclinical-targeting-of-aggressive-t-cell-malignancies-using-anti-cd5-chimeric-antigen-receptor
#18
K H Chen, M Wada, K G Pinz, H Liu, K-W Lin, A Jares, A E Firor, X Shuai, H Salman, M Golightly, F Lan, L Senzel, L-H Leung, X Jiang, Y Ma
The outlook for T-cell malignancies remain poor due to the lack of effective therapeutic options. Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies, however, designing CARs for T-cell based disease remain a challenge due to the shared surface antigen pool between normal and malignant T-cells. Normal T-cells express CD5 but NK (natural killer) cells do not, positioning NK cells as attractive cytotoxicity cells for CD5CAR design. Additionally, CD5 is highly expressed in T cell acute lymphoblastic leukemia (T-ALL) and peripheral T cell lymphomas (PTCLs)...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074065/hdac3-activity-is-required-for-initiation-of-leukemogenesis-in-acute-promyelocytic-leukemia
#19
P Mehdipour, F Santoro, O A Botrugno, M Romanenghi, C Pagliuca, G M Matthews, R W Johnstone, S Minucci
Leukemia accepted article preview online, 11 January 2017. doi:10.1038/leu.2017.3.
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28074064/o-glcnacylation-of-stat5-controls-tyrosine-phosphorylation-and-oncogenic-transcription-in-stat5-dependent-malignancies
#20
P Freund, M A Kerenyi, M Hager, T Wagner, B Wingelhofer, H T T Pham, M Elabd, X Han, P Valent, F Gouilleux, V Sexl, O H Krämer, B Groner, R Moriggl
The signal transducer and activator of transcription 5 (STAT5) regulates differentiation, survival, proliferation and transformation of hematopoietic cells. Upon cytokine stimulation, STAT5 tyrosine phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. Posttranslational modifications might contribute to enhanced STAT5 activation in the context of transformation, but the strength and duration of pYSTAT5 are incompletely understood...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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