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https://www.readbyqxmd.com/read/28228714/narrative-organization-deficit-in-lewy-body-disorders-is-related-to-alzheimer-pathology
#1
Murray Grossman, David J Irwin, Charles Jester, Amy Halpin, Sharon Ash, Katya Rascovsky, Daniel Weintraub, Corey T McMillan
Background: Day-to-day interactions depend on conversational narrative, and we examine here the neurobiological basis for difficulty organizing narrative discourse in patients with Lewy body disorders (LBD). Method: Narrative organization was examined in 56 non-aphasic LBD patients, including a non-demented cohort (n = 30) with Parkinson's disease (PD) or PD-Mild Cognitive Impairment PD-MCI,) and a cohort with mild dementia (n = 26) including PD-dementia (PDD) and dementia with Lewy bodies (DLB), with similar age and education but differing in MMSE (p < 0...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28228281/dysregulation-of-the-cytokine-gm-csf-induces-spontaneous-phagocyte-invasion-and-immunopathology-in-the-central-nervous-system
#2
Sabine Spath, Juliana Komuczki, Mario Hermann, Pawel Pelczar, Florian Mair, Bettina Schreiner, Burkhard Becher
Chronic inflammatory diseases are influenced by dysregulation of cytokines. Among them, granulocyte macrophage colony stimulating factor (GM-CSF) is crucial for the pathogenic function of T cells in preclinical models of autoimmunity. To study the impact of dysregulated GM-CSF expression in vivo, we generated a transgenic mouse line allowing the induction of GM-CSF expression in mature, peripheral helper T (Th) cells. Antigen-independent GM-CSF release led to the invasion of inflammatory myeloid cells into the central nervous system (CNS), which was accompanied by the spontaneous development of severe neurological deficits...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28228272/commanding-cns-invasion-gm-csf
#3
Junjie Zhao, Lillian Sun, Xiaoxia Li
Granulocyte-macrophage colony-stimulating factor (GM-CSF or Csf-2) is a pro-inflammatory mediator implicated in the pathogenesis of various autoimmune diseases. In this issue of Immunity, Spath et al. (2017) show that the dysregulated production of GM-CSF rather than IL-17 induces spontaneous immunopathology in a mouse model of CNS inflammation.
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28226856/evaluation-of-the-electric-field-in-the-brain-during-transcranial-direct-current-stimulation-a-sensitivity-analysis
#4
Laura Santos, Miguel Martinho, Ricardo Salvador, Cornelia Wenger, Sofia R Fernandes, Oscar Ripolles, Giulio Ruffini, Pedro C Miranda, Laura Santos, Miguel Martinho, Ricardo Salvador, Cornelia Wenger, Sofia R Fernandes, Oscar Ripolles, Giulio Ruffini, Pedro C Miranda, Laura Santos, Miguel Martinho, Cornelia Wenger, Ricardo Salvador, Oscar Ripolles, Giulio Ruffini, Sofia R Fernandes, Pedro C Miranda
The use of computational modeling studies accounts currently for the best approach to predict the electric field (E-field) distribution in transcranial direct current stimulation. As with any model, the values attributed to the physical properties, namely the electrical conductivity of the tissues, affect the predicted E-field distribution. A wide range of values for the conductivity of most tissues is reported in the literature. In this work, we used the finite element method to compute the E-field induced in a realistic human head model for two electrode montages targeting the left dorso-lateral prefrontal cortex (DLPFC)...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225337/multiple-cytokines-for-the-detection-of-mycobacterium-tuberculosis-infection-in-children-with-tuberculosis
#5
N Nausch, C Lundtoft, G Schulz, H Henckel, E Mayatepek, B Fleischer, F M Marx, M Jacobsen
SETTING: Interferon-gamma (IFN-γ) release assays (IGRAs) play an important role in the diagnosis of Mycobacterium tuberculosis infection. However, in children with tuberculosis (TB), some studies have shown increased frequencies of false-negative or indeterminate IGRA results. OBJECTIVE: To analyse the spectrum of different cytokines to improve the diagnostic accuracy of IGRAs in latent tuberculous infection (LTBI) and active TB. DESIGN: We performed multiplex cytokine expression analysis of QuantiFERON® Gold In-Tube supernatants in children with active TB (n = 21) and disease-free contacts with (n = 15) and without LTBI (n = 12), to determine the sensitivity and specificity of the modified tests...
March 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28222797/melanoma-antigen-specific-effector-t-cell-cytokine-secretion-patterns-in-patients-treated-with-ipilimumab
#6
Yana G Najjar, Fei Ding, Yan Lin, Robert VanderWeele, Lisa H Butterfield, Ahmad A Tarhini
BACKGROUND: In a previously reported study, patients with regionally advanced melanoma were treated with neoadjuvant ipilimumab (ipi) (Tarhini in PLoS ONE 9(2): e87705, 3). Significant changes in circulating myeloid derived suppressor cells (MDSC), regulatory T cells (Treg) and peptide specific type I CD4(+) and CD8(+) T cells were noted at week 6 that correlated with clinical outcome. Characterization of antigen-specific effector T cell secreted cytokines may shed insights into ipi associated T cell activation and function...
February 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28222766/increased-cortical-lesion-load-and-intrathecal-inflammation-is-associated-with-oligoclonal-bands-in-multiple-sclerosis-patients-a-combined-csf-and-mri-study
#7
Gabriele Farina, Roberta Magliozzi, Marco Pitteri, Richard Reynolds, Stefania Rossi, Alberto Gajofatto, Maria Donata Benedetti, Francesco Facchiano, Salvatore Monaco, Massimiliano Calabrese
BACKGROUND: Although IgG oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) are a frequent phenomenon in multiple sclerosis (MS) patients, their relationship with grey matter lesions, intrathecal/meningeal inflammation and clinical evolution has not been clarified yet. The aim of our study was to assess the relationship between the OCBs, the inflammatory/neurodegenerative CSF profile at diagnosis, the cortical lesion load and the clinical evolution after 10 years. METHODS: This is a 10-year observational, cross-sectional study based on a combined MRI, cognitive and CSF profiling of the examined patients...
February 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28220120/neutrophil-extracellular-traps-and-its-implications-in-inflammation-an-overview
#8
REVIEW
Vidal Delgado-Rizo, Marco A Martínez-Guzmán, Liliana Iñiguez-Gutierrez, Alejandra García-Orozco, Anabell Alvarado-Navarro, Mary Fafutis-Morris
In addition to physical barriers, neutrophils are considered a part of the first line of immune defense. They can be found in the bloodstream, with a lifespan of 6-8 h, and in tissue, where they can last up to 7 days. The mechanisms that neutrophils utilize for host defense are phagocytosis, degranulation, cytokine production, and, the most recently described, neutrophil extracellular trap (NET) production. NETs are DNA structures released due to chromatin decondensation and spreading, and they thus occupy three to five times the volume of condensed chromatin...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28218904/the-protumorigenic-potential-of-fty720-by-promoting-extramedullary-hematopoiesis-and-mdsc-accumulation
#9
Y Li, T Zhou, Y Wang, C Ning, Z Lv, G Han, J C Morris, E N Taylor, R Wang, H Xiao, C Hou, Y Ma, B Shen, J Feng, R Guo, Y Li, G Chen
FTY720 (also called fingolimod) is recognized as an immunosuppressant and has been approved by the Food and Drug Administration to treat refractory multiple sclerosis. However, long-term administration of FTY720 potentially increases the risk for cancer in recipients. The underlying mechanisms remain poorly understood. Herein, we provided evidence that FTY720 administration potentiated tumor growth. Mechanistically, FTY720 enhanced extramedullary hematopoiesis and massive accumulation of myeloid-derived suppressor cells (MDSCs), which actively suppressed antitumor immune responses...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28216876/wheatgrass-extract-ameliorates-hypoxia-induced-mucin-gene-expression-in-a549-cells
#10
Ju Hwan Sim, Moon-Hee Choi, Hyun-Jae Shin, Ji-Eun Lee
BACKGROUND: Wheatgrass is known to have antioxidant, antiaging, and anti-inflammatory effect. However, its protective effect against hypoxia is not yet evaluated. OBJECTIVE: In this study, we evaluated the protective and anti-inflammatory effect of wheatgrass against the hypoxia in airway epithelial cells. MATERIALS AND METHODS: A549 human lung adenocarcinoma cells were incubated in a hypoxic condition (CO2 5%/O2 1%) for 24 hr in the presence of different concentration of wheatgrass 50, 75, 100, and 150 μg/mL, and the magnitude of each immunologic response produced by the A549 cells was compared...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28213794/selected-cytokine-pathways-in-rheumatoid-arthritis
#11
REVIEW
Mélissa Noack, Pierre Miossec
Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction. Cytokines play a key role in its pathogenesis. They contribute to the induction and maintenance of inflammation and thus provide therapeutic targets. Many cytokines are involved in RA, and this review focuses on a few critical ones: tumor necrosis factor (TNF), interleukin (IL)-6, IL-1, IL-17, and GM-CSF. TNF and IL-6 are both well-established targets in RA treatment, and new biologic agents are reaching the market. IL-1 represents a more complex cytokine as results in humans do not reach those in animal models...
February 17, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28213566/a-randomised-phase-iib-study-of-mavrilimumab-a-novel-gm-csf-receptor-alpha-monoclonal-antibody-in-the-treatment-of-rheumatoid-arthritis
#12
Gerd R Burmester, Iain B McInnes, Joel Kremer, Pedro Miranda, Mariusz Korkosz, Jiri Vencovsky, Andrea Rubbert-Roth, Eduardo Mysler, Matthew A Sleeman, Alex Godwood, Dominic Sinibaldi, Xiang Guo, Wendy I White, Bing Wang, Chi-Yuan Wu, Patricia C Ryan, David Close, Michael E Weinblatt
OBJECTIVES: Despite the therapeutic value of current rheumatoid arthritis (RA) treatments, agents with alternative modes of action are required. Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor-α, was evaluated in patients with moderate-to-severe RA. METHODS: In a phase IIb study (NCT01706926), patients with inadequate response to ≥1 synthetic disease-modifying antirheumatic drug(s), Disease Activity Score 28 (DAS28)-C reactive protein (CRP)/erythrocyte sedimentation rate ≥3...
February 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28212655/elderly-onset-hereditary-pulmonary-alveolar-proteinosis-and-its-cytokine-profile
#13
Masayuki Ito, Kazuyuki Nakagome, Hiromitsu Ohta, Keiichi Akasaka, Yoshitaka Uchida, Atsushi Hashimoto, Ayako Shiono, Toshinori Takada, Makoto Nagata, Jun Tohyama, Koichi Hagiwara, Minoru Kanazawa, Koh Nakata, Ryushi Tazawa
BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by surfactant accumulation, and is caused by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. Abnormalities in CSF2 receptor alpha (CSF2RA) were reported to cause pediatric hereditary PAP. We report here the first case of CSF2RA-mutated, elderly-onset hereditary (h) PAP. CASE PRESENTATION: The patient developed dyspnea on exertion, and was diagnosed with PAP at the age of 77 years, based on findings from chest computed tomography scan and bronchoalveolar lavage...
February 17, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28205361/immunotherapy-against-metastatic-bladder-cancer-by-combined-administration-of-granulocyte-macrophage-colony-stimulating-factor-and-interleukin-2-surface-modified-mb49-bladder-cancer-stem-cells-vaccine
#14
Chun-Yan Wang, Rui Hua, Li Liu, Xiaomin Zhan, Simei Chen, Song Quan, Qing-Jun Chu, Yong-Tong Zhu
In previous studies, it has been shown that the granulocyte macrophage-colony stimulating factor (GM-CSF) or interleukin-2 (IL-2) surface modified MB49 bladder cancer stem cells (MCSCs) vaccine could induce a specific antitumor immunity and against bladder cancer in mice model respectively. However, whether combined administration of GM-CSF and IL-2 could produce specific immune responses to cancer stem cells (CSCs) was uncertain. MCSCs were established and characterized. GM-CSF and IL-2 MCSCs vaccines were prepared and bioactivity was evaluated...
February 16, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28202867/gm-csf-autoantibody-positive-pulmonary-alveolar-proteinosis-with-simultaneous-myeloproliferative-neoplasm
#15
Naoto Imoto, Nakashima Harunori, Katsuya Furukawa, Naoyuki Tange, Atsushi Murase, Masaya Hayakawa, Masatoshi Ichihara, Yosuke Iwata, Hiroshi Kosugi
Pulmonary alveolar proteinosis (PAP) is classified as autoimmune, secondary, or genetic. We herein describe a 69-year-old man with autoimmune PAP, simultaneously diagnosed with myeloproliferative neoplasm (MPN). Two years after the diagnosis, the MPN progressed to acute myeloid leukemia, and the patient died from an alveolar hemorrhage during remission induction chemotherapy. Throughout the clinical course, no progression of PAP was observed, despite the progression to leukemia. There are few reports of autoimmune PAP with hematological malignancy, and this case demonstrated that an evaluation for GM-CSF autoantibodies is important for distinguishing the autoimmune and secondary forms of PAP, even if the patient has hematological malignancy...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28194282/localizing-age-related-changes-in-brain-structure-using-voxel-based-morphometry
#16
Shu Hua Mu, Min Xu, Jun Xiu Duan, Jian Zhang, Li Hai Tan
Aim. We report the dynamic anatomical sequence of human cortical gray matter development from late childhood to young adults using VBM and ROI-based methods. Method. The structural MRI of 91 normal individuals ranging in age from 6 to 26 years was obtained and the GMV for each region was measured. Results. Our results showed that the earliest loss of GMV occurred in left olfactory, right precuneus, caudate, left putamen, pallidum, and left middle temporal gyrus. In addition, the trajectory of maturational and aging showed a linear decline in GMV on both cortical lobes and subcortical regions...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28193830/il-6-regulates-m2-polarization-and-local-proliferation-of-adipose-tissue-macrophages-in-obesity
#17
Julia Braune, Ulrike Weyer, Constance Hobusch, Jan Mauer, Jens C Brüning, Ingo Bechmann, Martin Gericke
Obesity is associated with chronic low-grade inflammation of adipose tissue (AT) and an increase of AT macrophages (ATMs) that is linked to the onset of type 2 diabetes. We have recently shown that focal sites of inflammation around dying adipocytes, so-called crown-like structures, exhibit a unique microenvironment for macrophage proliferation. Interestingly, locally proliferating macrophages were not classically activated (M1), but they exhibited a rather alternatively activated (M2) immune phenotype. In this study, we established organotypic cell cultures of AT explants to study the impact of cytokine treatment on local ATM proliferation, without the bias of early monocyte recruitment...
February 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28193627/adoptive-transfer-of-invariant-nkt-cells-as-immunotherapy-for-advanced-melanoma-a-phase-1-clinical-trial
#18
Mark A Exley, Philip Friedlander, Nadia Alatrakchi, Lianne Vriend, Simon C Yue, Tetsuro Sasada, Wanyong Zang, Yo Mizukami, Justice Clark, David Nemer, Ken LeClair, Christine Canning, Heather Daley, Glenn Dranoff, Anita Giobbie-Hurder, F Stephen Hodi, Jerome Ritz, Steven P Balk
PURPOSE: Invariant NKT cells (iNKT) are innate-like CD1d-restricted T cells with immunoregulatory activity in diseases including cancer. iNKT from advanced cancer patients can have reversible defects including IFNγ production, and iNKT IFNγ production may stratify for survival. Previous clinical trials using iNKT cell activating ligand α-galactosylceramide have shown responses. Therefore, a phase 1 clinical trial was performed of autologous in vitro expanded iNKT cells in stage IIIB-IV melanoma...
February 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28188918/evaluation-of-multimodal-segmentation-based-on-3d-t1-t2-and-flair-weighted-images-the-difficulty-of-choosing
#19
Tobias Lindig, Raviteja Kotikalapudi, Daniel Schweikardt, Pascal Martin, Friedemann Bender, Uwe Klose, Ulrike Ernemann, Niels K Focke, Benjamin Bender
Voxel-based morphometry is still mainly based on T1-weighted MRI scans. Misclassification of vessels and dura mater as gray matter has been previously reported. Goal of the present work was to evaluate the effect of multimodal segmentation methods available in SPM12, and their influence on identification of age related atrophy and lesion detection in epilepsy patients. 3D T1-, T2- and FLAIR-images of 77 healthy adults (mean age 35.8 years, 19-66 years, 45 females), 7 patients with malformation of cortical development (MCD) (mean age 28...
February 7, 2017: NeuroImage
https://www.readbyqxmd.com/read/28186996/harnessing-rna-sequencing-for-global-unbiased-evaluation-of-two-new-adjuvants-for-dendritic-cell-immunotherapy
#20
Till S M Mathan, Johannes Textor, Annette E Sköld, Inge Reinieren-Beeren, Tom van Oorschot, Mareke Brüning, Carl G Figdor, Sonja I Buschow, Ghaith Bakdash, I Jolanda M de Vries
Effective stimulation of immune cells is crucial for the success of cancer immunotherapies. Current approaches to evaluate the efficiency of stimuli are mainly defined by known flow cytometry-based cell activation or cell maturation markers. This method however does not give a complete overview of the achieved activation state and may leave important side effects unnoticed. Here, we used an unbiased RNA sequencing (RNA-seq)-based approach to compare the capacity of four clinical-grade dendritic cell (DC) activation stimuli used to prepare DC-vaccines composed of various types of DC subsets; the already clinically applied GM-CSF and Frühsommer meningoencephalitis (FSME) prophylactic vaccine and the novel clinical grade adjuvants protamine-RNA complexes (pRNA) and CpG-P...
February 8, 2017: Oncotarget
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