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https://www.readbyqxmd.com/read/28334938/clinical-and-genetic-characterization-of-leukoencephalopathies-in-adults
#1
David S Lynch, Anderson Rodrigues Brandão de Paiva, Wei Jia Zhang, Enrico Bugiardini, Fernando Freua, Leandro Tavares Lucato, Lucia Inês Macedo-Souza, Rahul Lakshmanan, Justin A Kinsella, Aine Merwick, Alexander M Rossor, Nin Bajaj, Brian Herron, Paul McMonagle, Patrick J Morrison, Deborah Hughes, Alan Pittman, Matilde Laurà, Mary M Reilly, Jason D Warren, Catherine J Mummery, Jonathan M Schott, Matthew Adams, Nick C Fox, Elaine Murphy, Indran Davagnanam, Fernando Kok, Jeremy Chataway, Henry Houlden
Leukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration of cerebral white matter. They are associated with a spectrum of clinical phenotypes dominated by dementia, psychiatric changes, movement disorders and upper motor neuron signs. Mutations in at least 60 genes can lead to leukoencephalopathy with often overlapping clinical and radiological presentations. For these reasons, patients with genetic leukoencephalopathies often endure a long diagnostic odyssey before receiving a definitive diagnosis or may receive no diagnosis at all...
March 2, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28319612/colony-stimulating-factor-1-receptor-is-a-central-component-of-the-foreign-body-response-to-biomaterial-implants-in-rodents-and-non-human%C3%A2-primates
#2
Joshua C Doloff, Omid Veiseh, Arturo J Vegas, Hok Hei Tam, Shady Farah, Minglin Ma, Jie Li, Andrew Bader, Alan Chiu, Atieh Sadraei, Stephanie Aresta-Dasilva, Marissa Griffin, Siddharth Jhunjhunwala, Matthew Webber, Sean Siebert, Katherine Tang, Michael Chen, Erin Langan, Nimit Dholokia, Raj Thakrar, Meirigeng Qi, Jose Oberholzer, Dale L Greiner, Robert Langer, Daniel G Anderson
Host recognition and immune-mediated foreign body response to biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not. Macrophages, via CXCL13, lead to downstream B cell recruitment, which further potentiated fibrosis, as confirmed by B cell knockout and CXCL13 neutralization...
March 20, 2017: Nature Materials
https://www.readbyqxmd.com/read/28286294/specific-suppression-of-microgliosis-cannot-circumvent-the-severe-neuropathology-in-peroxisomal-%C3%AE-oxidation-deficient-mice
#3
L Beckers, S Stroobants, S Verheijden, B West, R D'Hooge, M Baes
An important hallmark of various neurodegenerative disorders is the proliferation and activation of microglial cells, the resident immune cells of the central nervous system (CNS). Mice that lack multifunctional protein-2 (MFP2), the key enzyme in peroxisomal β-oxidation, develop excessive microgliosis that positively correlates with behavioral deficits whereas no neuronal loss occurs. However, the precise contribution of neuroinflammation to the fatal neuropathology of MFP2 deficiency remains largely unknown...
March 7, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28273719/depletion-of-microglia-exacerbates-postischemic-inflammation-and-brain-injury
#4
Wei-Na Jin, Samuel Xiang-Yu Shi, Zhiguo Li, Minshu Li, Kristofer Wood, Rayna J Gonzales, Qiang Liu
Brain ischemia elicits microglial activation and microglia survival depend on signaling through colony-stimulating factor 1 receptor (CSF1R). Although depletion of microglia has been linked to worse stroke outcomes, it remains unclear to what extent and by what mechanisms activated microglia influence ischemia-induced inflammation and injury in the brain. Using a mouse model of transient focal cerebral ischemia and reperfusion, we demonstrated that depletion of microglia via administration of the dual CSF1R/c-Kit inhibitor PLX3397 exacerbates neurodeficits and brain infarction...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28273455/a-bach2-cebp-gene-regulatory-network-for-the-commitment-of-multipotent-hematopoietic-progenitors
#5
Ari Itoh-Nakadai, Mitsuyo Matsumoto, Hiroki Kato, Junichi Sasaki, Yukihiro Uehara, Yuki Sato, Risa Ebina-Shibuya, Mizuho Morooka, Ryo Funayama, Keiko Nakayama, Kyoko Ochiai, Akihiko Muto, Kazuhiko Igarashi
Hematopoietic stem cell and multipotent progenitor (MPP) commitment can be tuned in response to an infection so that their differentiation is biased toward myeloid cells. Here, we find that Bach2, which inhibits myeloid differentiation in common lymphoid progenitors, represses a cohort of myeloid genes and activates those linked to lymphoid function. Bach2 repressed both Cebpb and its target Csf1r, encoding C/EBPβ and macrophage colony-stimulating factor receptor (M-CSFr), respectively, whereas C/EBPβ repressed Bach2 and activated Csf1r...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28272478/erythro-myeloid-progenitors-can-differentiate-from-endothelial-cells-and-modulate-embryonic-vascular-remodeling
#6
Bahar Kasaai, Vincenza Caolo, Hanna M Peacock, Stephanie Lehoux, Elisa Gomez-Perdiguero, Aernout Luttun, Elizabeth A V Jones
Erythro-myeloid progenitors (EMPs) were recently described to arise from the yolk sac endothelium, just prior to vascular remodeling, and are the source of adult/post-natal tissue resident macrophages. Questions remain, however, concerning whether EMPs differentiate directly from the endothelium or merely pass through. We provide the first evidence in vivo that EMPs can emerge directly from endothelial cells (ECs) and demonstrate a role for these cells in vascular development. We find that EMPs express most EC markers but late EMPs and EMP-derived cells do not take up acetylated low-density lipoprotein (AcLDL), as ECs do...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28251674/microglial-repopulation-resolves-inflammation-and-promotes-brain-recovery-after-injury
#7
Rachel A Rice, Jason Pham, Rafael J Lee, Allison R Najafi, Brian L West, Kim N Green
Microglia mediate chronic neuroinflammation following central nervous system (CNS) disease or injury, and in doing so, damage the local brain environment by impairing recovery and contributing to disease processes. Microglia are critically dependent on signaling through the colony-stimulating factor 1 receptor (CSF1R) and can be eliminated via administration of CSF1R inhibitors. Resolving chronic neuroinflammation represents a universal goal for CNS disorders, but long-term microglial elimination may not be amenable to clinical use...
March 2, 2017: Glia
https://www.readbyqxmd.com/read/28236968/regulation-of-embryonic-and-postnatal-development-by-the-csf-1-receptor
#8
Violeta Chitu, E Richard Stanley
Macrophages are found in all tissues and regulate tissue morphogenesis during development through trophic and scavenger functions. The colony stimulating factor-1 (CSF-1) receptor (CSF-1R) is the major regulator of tissue macrophage development and maintenance. In combination with receptor activator of nuclear factor κB (RANK), the CSF-1R also regulates the differentiation of the bone-resorbing osteoclast and controls bone remodeling during embryonic and early postnatal development. CSF-1R-regulated macrophages play trophic and remodeling roles in development...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28191455/ankylosing-spondylitis-patients-have-impaired-osteoclast-gene-expression-in-circulating-osteoclast-precursors
#9
Inês P Perpétuo, Joana Caetano-Lopes, Elsa Vieira-Sousa, Raquel Campanilho-Marques, Cristina Ponte, Helena Canhão, Mari Ainola, João E Fonseca
INTRODUCTION: Ankylosing spondylitis (AS) is typically characterized by focal bone overgrowth and also by systemic bone loss. We hypothesize that the increased osteoproliferation found in AS might be partially due to reduced ability of osteoclast precursors (OCPs) to differentiate into osteoclasts (OCs). Therefore, our aim was to characterize bone remodeling and pro-osteoclastogenesis inflammatory environment, monocytes' phenotype, and in vitro osteoclast differentiation in AS patients...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28128708/detection-of-stem-cell-transplant-rejection-with-ferumoxytol-mr-imaging-correlation-of-mr-imaging-findings-with-those-at-intravital-microscopy
#10
Heike E Daldrup-Link, Carmel Chan, Olga Lenkov, Seyedmeghdad Taghavigarmestani, Toktam Nazekati, Hossein Nejadnik, Fanny Chapelin, Aman Khurana, Xinming Tong, Fan Yang, Laura Pisani, Michael Longaker, Sanjiv Sam Gambhir
Purpose To determine whether endogenous labeling of macrophages with clinically applicable nanoparticles enables noninvasive detection of innate immune responses to stem cell transplants with magnetic resonance (MR) imaging. Materials and Methods Work with human stem cells was approved by the institutional review board and the stem cell research oversight committee, and animal experiments were approved by the administrative panel on laboratory animal care. Nine immunocompetent Sprague-Dawley rats received intravenous injection of ferumoxytol, and 18 Jax C57BL/6-Tg (Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6) 2Bck/J mice received rhodamine-conjugated ferumoxytol...
January 27, 2017: Radiology
https://www.readbyqxmd.com/read/28116522/molecular-characterization-of-cd44-cd24-ck-cd45-cells-in-benign-and-malignant-breast-lesions
#11
Arnaud Da Cruz Paula, Catarina Leitão, Oriana Marques, Ana Margarida Rosa, Ana Helena Santos, Alexandra Rêma, Maria de Fátima Faria, Ana Rocha, José Luís Costa, Margarida Lima, Carlos Lopes
Breast cancer epithelial cells with the CD44(+)/CD24(-/low) phenotype possess tumor-initiating cells and epithelial-mesenchymal transition (EMT) capacity. Massive parallel sequencing can be an interesting approach to deepen the molecular characterization of these cells. We characterized CD44(+)/CD24(-)/cytokeratin(Ck)(+)/CD45(-) cells isolated through flow cytometry from 43 biopsy and 6 mastectomy samples harboring different benign and malignant breast lesions. The Ion Torrent Ampliseq Cancer Hotspot panel v2 (CHPv2) was used for the identification of somatic mutations in the DNA extracted from isolated CD44(+)/CD24(-)/Ck(+)/CD45(-) cells...
March 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28099906/genomic-characteristics-of-pancreatic-squamous-cell-carcinoma-an-investigation-by-using-high-throughput-sequencing-after-in-solution-hybrid-capture
#12
Meng-Dan Xu, Shu-Ling Liu, Yi-Zhong Feng, Qiang Liu, Meng Shen, Qiaoming Zhi, Zeyi Liu, Dong-Mei Gu, Jie Yu, Liu-Mei Shou, Fei-Ran Gong, Qi Zhu, Weiming Duan, Kai Chen, Junning Zhang, Meng-Yao Wu, Min Tao, Wei Li
Squamous cell carcinoma (SCC) of pancreas is a rare histotype of pancreatic ductal carcinoma which is distinct from pancreatic adenocarcinoma (AC). Although there are standard treatments for pancreatic AC, no precise therapies exist for pancreatic SCC. Here, we screened 1033 cases of pancreatic cancer and identified 2 cases of pure SCC, which were pathologically diagnosed on the basis of finding definite intercellular bridges and/or focal keratin peal formation in the tumor cells. Immunohistochemistry assay confirmed the positive expression of CK5/6 and p63 in pancreatic SCC...
January 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28057171/predicting-high-impact-pharmacological-targets-by-integrating-transcriptome-and-text-mining-features
#13
Anatoly Mayburd, Ancha Baranova
PURPOSE: Novel, "outside of the box" approaches are needed for evaluating candidate molecules, especially in oncology. Throughout the years of 2000-2010, the efficiency of drug development fell to barely acceptable levels, and in the second decade of this century, levels have improved only marginally. This dismal condition continues despite unprecedented progress in the development of a variety of high-throughput tools, computational methods, aggregated databases, drug repurposing programs and innovative chemistries...
October 2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28025469/mr-spectroscopy-in-patients-with-hereditary-diffuse-leukoencephalopathy-with-spheroids-and-asymptomatic-carriers-of-colony-stimulating-factor-1-receptor-mutation
#14
Takashi Abe, Toshitaka Kawarai, Koji Fujita, Wataru Sako, Yuka Terasawa, Tsuyoshi Matsuda, Waka Sakai, Ai Tsukamoto-Miyashiro, Naoko Matsui, Yuishin Izumi, Ryuji Kaji, Masafumi Harada
PURPOSE: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare neurodegenerative disorder with various clinical presentations. Mutation of the colony-stimulating factor 1 receptor (CSF1R) gene is considered to be a cause of this autosomal dominant disorder. The purpose of this study was to report magnetic resonance spectroscopy (MRS) findings in patients with HDLS and asymptomatic carriers and to clarify the use of MRS in this disease. MATERIALS AND METHODS: In this retrospective, institutional review board-approved study, we included four consecutive patients, genetically diagnosed with HDLS, and two asymptomatic carriers after acquiring informed consent...
December 26, 2016: Magnetic Resonance in Medical Sciences: MRMS
https://www.readbyqxmd.com/read/27988109/receptor-tyrosine-kinases-translocation-partners-in-hematopoietic-disorders
#15
REVIEW
Katelyn N Nelson, Malalage N Peiris, April N Meyer, Asma Siari, Daniel J Donoghue
Receptor tyrosine kinases (RTKs) activate various signaling pathways and regulate cellular proliferation, survival, migration, and angiogenesis. Malignant neoplasms often circumvent or subjugate these pathways by promoting RTK overactivation through mutation or chromosomal translocation. RTK translocations create a fusion protein containing a dimerizing partner fused to an RTK kinase domain, resulting in constitutive kinase domain activation, altered RTK cellular localization, upregulation of downstream signaling, and novel pathway activation...
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27956588/modeling-synovial-sarcoma-metastasis-in-the-mouse-pi3-lipid-signaling-and-inflammation
#16
Jared J Barrott, Lisa A Kafchinski, Huifeng Jin, Jared W Potter, Sarmishta D Kannan, Robert Kennedy, Tim Mosbruger, Wei-Lien Wang, Jen-Wei Tsai, Dejka M Araujo, Ting Liu, Mario R Capecchi, Alexander J Lazar, Kevin B Jones
Solid tumor metastasis is a complex biology, impinged upon by a variety of dysregulated signaling pathways. PI3'-lipid signaling has been associated with metastasis and inflammation in many cancers, but the relationship between tumor cell-intrinsic PI3'-lipid signaling and inflammatory cell recruitment has remained enigmatic. Elevated PI3'-lipid signaling associates with progression of synovial sarcoma, a deadly soft tissue malignancy initiated by a t(X;18) chromosomal translocation that generates an SS18-SSX fusion oncoprotein...
December 12, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27914067/5q-syndrome-like-features-as-the-first-manifestation-of-myelodysplastic-syndrome-in-a-patient-with-an-unbalanced-whole-arm-translocation-der-5-19-p10-q10
#17
Hiroshi Ureshino, Haruna Kizuka, Kana Kusaba, Haruhiko Sano, Atsujiro Nishioka, Takero Shindo, Yasushi Kubota, Toshihiko Ando, Kensuke Kojima, Shinya Kimura
Derivative (5;19)(p10;q10) [der(5;19)(p10;q10)] is a rare chromosomal abnormality in myelodysplastic syndrome (MDS), and is genetically similar to deletion 5q [del(5q)]. However, MDS with der(5;19)(p10;q10) and 5q- syndrome are generally characterized as distinct subtypes. Here, we report a case of a patient with 5q- syndrome-like features as the first manifestation of MDS with der(5; 19)(p10;q10). A 59-year-old woman was admitted to our hospital for anemia without leukopenia and thrombocytopenia. She had received chemotherapy comprising carboplatin and docetaxel for endometrial cancer eight years before...
December 2, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27898738/receptor-type-protein-tyrosine-phosphatase-%C3%AE-and-colony-stimulating-factor-1-receptor-in-the-intestine-cellular-expression-and-cytokine-and-chemokine-responses-by-interleukin-34-and-colony-stimulating-factor-1
#18
Stephanie Zwicker, Daniela Bureik, Madeleen Bosma, Gisele Lago Martinez, Sven Almer, Elisabeth A Boström
Differential intestinal expression of the macrophage growth factors colony stimulating factor-1 (CSF-1), interleukin (IL)-34, and their shared CSF-1 receptor (CSF-1R) in inflammatory bowel disease (IBD) has been shown. Diverse expression between CSF-1 and IL-34, suggest that IL-34 may signal via an alternate receptor. Receptor-type protein-tyrosine phosphatase ζ (PTPRZ1, RPTP-ζ), an additional IL-34 receptor, was recently identified. Here, we aimed to assess PTPRZ1 expression in IBD and non-IBD intestinal biopsies...
2016: PloS One
https://www.readbyqxmd.com/read/27859676/microglia-and-brain-macrophages-an-update
#19
REVIEW
Atsushi Sasaki
Current immunohistochemical techniques have made the identification of microglia possible in routinely processed tissue sections from human brains. Previous studies have indicated that almost no neurological diseases exist without microglial activation. Activated microglia often secrete inflammatory cytokines in various diseases, including Alzheimer's disease, but microglial activation is not always associated with inflammation. The equation microglial activation means "neuroinflammation" is absurd and misleading...
November 18, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/27846891/cytokine-and-chemokine-alterations-in-tissue-csf-and-plasma-in-early-presymptomatic-phase-of-experimental-allergic-encephalomyelitis-eae-in-a-rat-model-of-multiple-sclerosis
#20
Nozha Borjini, Mercedes Fernández, Luciana Giardino, Laura Calzà
BACKGROUND: Experimental allergic encephalomyelitis (EAE) is the most commonly used experimental animal model for human multiple sclerosis (MS) that has been used so far to study the acute and remission-relapsing phases of the disease. Despite the vast literature on neuroinflammation onset and progression in EAE, important questions are still open regarding in particular the early asymptomatic phase between immunization and clinical onset. METHODS: In this study, we performed a time-course investigation of neuroinflammation and demyelination biomarkers in the spinal cord (SC), cerebrospinal fluid (CSF), and blood in EAE induced in dark agouti (DA) female rats compared to the controls and adjuvant-injected rats, using high-throughput technologies for gene expression and protein assays and focusing on the time-course between immunization, clinical onset (1, 5, 8 days post-immunization (DPI)), and progression (11 and 18 DPI)...
November 15, 2016: Journal of Neuroinflammation
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