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https://www.readbyqxmd.com/read/29774053/postherpes-simplex-encephalitis-a-case-series-of-viral-triggered-autoimmunity-synaptic-autoantibodies-and-response-to-therapy
#1
Harry Alexopoulos, Sofia Akrivou, Sotiria Mastroyanni, Maria Antonopoulou, Argirios Dinopoulos, Melpo Giorgi, Kostas Konstantinou, Evangelos Kouremenos, Maria Lariou, Dimitrios Naoumis, Efterpi Pavlidou, Evaggelos Pavlou, Konstantinos Voudris, Panayotis Vlachoyiannopoulos, Marinos C Dalakas
Background: Recent evidence suggests that patients with herpes simplex virus (HSV) encephalitis may relapse because of autoimmunity against the N-methyl-D-aspartate receptor (NMDAR). We present a case series of post-HSV relapsing encephalopathy associated with antibodies to central nervous system (CNS) synaptic antigens. Patient/Methods: Sera and cerebrospinal fluid (CSF) from five patients with HSV encephalitis who relapsed after antiviral therapy were tested for anti-NMDAR, gamma-aminobutyric acid b receptor (GABAbR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), Leucine-rich, glioma inactivated 1 (LGI1), anti -contactin-associated protein-like 2 (CASPR2) and dipeptidyl-peptidase-like protein-6 (DDPX) antibodies using cell-based assays...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29696018/overinterpretation-and-overtreatment-of-low-titer-antibodies-against-contactin-associated-protein-2
#2
Christian G Bien
Antibodies (abs) against neural or glial antigens have become important diagnostic markers of autoimmune encephalitides. A key requirement for interpretation of any test in clinical medicine is specificity. In this work, a 35-year-old female patient with low-titer contactin-associated protein-2 abs not satisfying clinical criteria of autoimmune encephalitis is reported. The patient had a recurrent depressive disorder and, at the time of the ab study, a moderate depressive episode. Overinterpretation and misinterpretation of patient's complaints and paraclinical study results fueled the idea of an autoimmune encephalitis...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29673312/overexpression-of-contactin-1-promotes-growth-migration-and-invasion-in-hs578t-breast-cancer-cells
#3
Nan Chen, Sai He, Jie Geng, Zhang-Jun Song, Pi-Hua Han, Juan Qin, Zheng Zhao, Yong-Chun Song, Hu-Xia Wang, Cheng-Xue Dang
BACKGROUND: Contactin1 (CNTN1) has been shown to play an important role in the invasion and metastasis of several tumors; however, the role of CNTN1 in breast cancer has not been fully studied. The purpose of this study is to investigate the role of CNTN1 in regulating tumor growth, migration and invasion in breast cancer. RESULTS: To investigate its function, CNTN1 was expressed in Hs578T cells. CNTN1 expression was confirmed by western blot, immunohistochemistry and real-time RT-PCR...
April 19, 2018: BMC Cell Biology
https://www.readbyqxmd.com/read/29610457/cntnap2-stabilizes-interneuron-dendritic-arbors-through-cask
#4
Ruoqi Gao, Nicolas H Piguel, Alexandria E Melendez-Zaidi, Maria Dolores Martin-de-Saavedra, Sehyoun Yoon, Marc P Forrest, Kristoffer Myczek, Gefei Zhang, Theron A Russell, John G Csernansky, D James Surmeier, Peter Penzes
Contactin associated protein-like 2 (CNTNAP2) has emerged as a prominent susceptibility gene implicated in multiple complex neurodevelopmental disorders, including autism spectrum disorders (ASD), intellectual disability (ID), and schizophrenia (SCZ). The presence of seizure comorbidity in many of these cases, as well as inhibitory neuron dysfunction in Cntnap2 knockout (KO) mice, suggests CNTNAP2 may be crucial for proper inhibitory network function. However, underlying cellular mechanisms are unclear. Here we show that cultured Cntnap2 KO mouse neurons exhibit an inhibitory neuron-specific simplification of the dendritic tree...
April 2, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29511214/author-correction-nanomechanics-of-multidomain-neuronal-cell-adhesion-protein-contactin-revealed-by-single-molecule-afm-and-smd
#5
Karolina Mikulska-Ruminska, Andrej J Kulik, Carine Benadiba, Ivet Bahar, Giovanni Dietler, Wieslaw Nowak
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
March 6, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29460173/changes-in-the-axo-glial-junctions-of-the-optic-nerves-of-cuprizone-treated-mice
#6
Wataru Kojima, Kensuke Hayashi
Demyelination induced by cuprizone in mice has served a useful model system for the study of demyelinating diseases, such as multiple sclerosis. Severity of demyelination by cuprizone, however, varies across different regions of the central nervous system; the corpus callosum is sensitive, while the optic nerves are resistant. Here, we investigated the effects of cuprizone on optic nerves, focusing on the axo-glial junctions. Immunostaining for sodium channels, contactin-associated protein, neurofascins, and potassium channels revealed that there were no massive changes in the density and morphology of the axo-glial junctions in cuprizone-treated optic nerves...
February 19, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29435918/plp1-gene-variation-modulates-leftward-and-rightward-functional-hemispheric-asymmetries
#7
Sebastian Ocklenburg, Wanda M Gerding, Maximilian Raane, Larissa Arning, Erhan Genç, Jörg T Epplen, Onur Güntürkün, Christian Beste
Molecular neurobiological factors determining corpus callosum physiology and anatomy have been suggested to be one of the major factors determining functional hemispheric asymmetries. Recently, it was shown that allelic variations in two myelin-related genes, the proteolipid protein 1 gene PLP1 and the contactin 1 gene CNTN1, are associated with differences in interhemispheric integration. Here, we investigated whether three single nucleotide polymorphisms that were associated with interhemispheric integration via the corpus callosum in a previous study also are relevant for functional hemispheric asymmetries...
February 13, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29429934/immune-or-genetic-mediated-disruption-of-caspr2-causes-pain-hypersensitivity-due-to-enhanced-primary-afferent-excitability
#8
John M Dawes, Greg A Weir, Steven J Middleton, Ryan Patel, Kim I Chisholm, Philippa Pettingill, Liam J Peck, Joseph Sheridan, Akila Shakir, Leslie Jacobson, Maria Gutierrez-Mecinas, Jorge Galino, Jan Walcher, Johannes Kühnemund, Hannah Kuehn, Maria D Sanna, Bethan Lang, Alex J Clark, Andreas C Themistocleous, Noboru Iwagaki, Steven J West, Karolina Werynska, Liam Carroll, Teodora Trendafilova, David A Menassa, Maria Pia Giannoccaro, Ester Coutinho, Ilaria Cervellini, Damini Tewari, Camilla Buckley, M Isabel Leite, Hendrik Wildner, Hanns Ulrich Zeilhofer, Elior Peles, Andrew J Todd, Stephen B McMahon, Anthony H Dickenson, Gary R Lewin, Angela Vincent, David L Bennett
Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absence of neural injury. We therefore investigated the mechanism by which CASPR2 modulates nociceptive function. Mice lacking CASPR2 (Cntnap2-/- ) demonstrated enhanced pain-related hypersensitivity to noxious mechanical stimuli, heat, and algogens...
February 21, 2018: Neuron
https://www.readbyqxmd.com/read/29368307/hashimoto-s-encephalopathy-presenting-as-pseudobulbar-palsy
#9
Gokcen Oz Tuncer, Serap Teber, Muhammed Gültekin Kutluk, Pelin Albayrak, Gülhis Deda
INTRODUCTION: Hashimoto's encephalopathy (HE) is an autoimmune condition with varied neurological and psychiatric features. HE is very unusual as a cause of pseudobulbar palsy (PSP). CASE PRESENTATION: A 14-year-old male was admitted with right-sided weakness, dysphagia, speech disorder, and aggressiveness. Brain magnetic resonance imaging showed increased intensity in bilateral temporal, insular cortex, amygdala, and parahippocampal area on T2-weighted and fluid-attenuated inversion recovery images...
January 24, 2018: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29300891/loss-of-cntnap2-causes-axonal-excitability-deficits-developmental-delay-in-cortical-myelination-and-abnormal-stereotyped-motor-behavior
#10
Ricardo Scott, Alberto Sánchez-Aguilera, Kim van Elst, Lynette Lim, Nathalie Dehorter, Sung Eun Bae, Giorgia Bartolini, Elior Peles, Martien J H Kas, Hilgo Bruining, Oscar Marín
Contactin-associated protein-like 2 (Caspr2) is found at the nodes of Ranvier and has been associated with physiological properties of white matter conductivity. Genetic variation in CNTNAP2, the gene encoding Caspr2, has been linked to several neurodevelopmental conditions, yet pathophysiological effects of CNTNAP2 mutations on axonal physiology and brain myelination are unknown. Here, we have investigated mouse mutants for Cntnap2 and found profound deficiencies in the clustering of Kv1-family potassium channels in the juxtaparanodes of brain myelinated axons...
December 28, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29297312/generation-of-megabase-scale-deletions-inversions-and-duplications-involving-the-contactin-6-gene-in-mice-by-crispr-cas9-technology
#11
Alexei N Korablev, Irina A Serova, Oleg L Serov
BACKGROUND: Copy Number Variation (CNV) of the human CNTN6 gene (encoding the contactin-6 protein), caused by deletions or duplications, is responsible for severe neurodevelopmental impairments, often in combination with facial dysmorphias. Conversely, deleterious point mutations of this gene do not show any clinical phenotypes. The aim of this study is to generate mice carrying large deletions, duplications and inversions involving the Cntn6 gene as a new experimental model to study CNV of the human CNTN6 locus...
December 28, 2017: BMC Genetics
https://www.readbyqxmd.com/read/29244234/mechanisms-of-caspr2-antibodies-in-autoimmune-encephalitis-and-neuromyotonia
#12
Kristina R Patterson, Josep Dalmau, Eric Lancaster
OBJECTIVE: To determine the pathogenic mechanisms of autoantibodies to the cell adhesion molecule Caspr2 in acquired neuromyotonia and autoimmune encephalitis. METHODS: Caspr2-positive samples were confirmed using a cell-based assay, and their IgG subtypes were determined by enzyme-linked immunosorbent assay and cell-based assay. A solid phase binding assay quantified the binding of Caspr2 to contactin-2 in the presence of Caspr2 autoantibodies. Living cultures of primary rat hippocampal neurons were incubated with Caspr2-positive or control sera, and the distribution of Caspr2-positive immunofluorescent puncta and total surface Caspr2 was quantified...
January 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29238462/mechanisms-of-spinal-cord-injury-regeneration-in-zebrafish-a-systematic-review
#13
REVIEW
Zeynab Noorimotlagh, Mahla Babaie, Mahdi Safdarian, Tahereh Ghadiri, Vafa Rahimi-Movaghar
Objectives: To determine the molecular and cellular mechanisms of spinal cord regeneration in zebrafish. Materials and Methods: Medical databases of PubMed and Scopus were searched with following key words: Zebrafish; spinal cord injuries; regeneration; recovery of function. The map of mechanisms was performed using Xmind software. Results: Wnt/ß-catenin signaling, L1.1, L1.2, Major vault protein (MVP), contactin-2 and High mobility group box1 (HMGB1) had positive promoting effects on axonal re-growth while Ptena had an inhibitory effect...
December 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29165835/the-function-of-contactin-2-tag-1-in-oligodendrocytes-in-health-and-demyelinating-pathology
#14
Lida Zoupi, Maria Savvaki, Katerina Kalemaki, Ilias Kalafatakis, Kyriaki Sidiropoulou, Domna Karagogeos
The oligodendrocyte maturation process and the transition from the pre-myelinating to the myelinating state are extremely important during development and in pathology. In the present study, we have investigated the role of the cell adhesion molecule CNTN2/TAG-1 on oligodendrocyte proliferation, differentiation, myelination, and function during development and under pathological conditions. With the combination of in vivo, in vitro, ultrastructural, and electrophysiological methods, we have mapped the expression of CNTN2 protein in the oligodendrocyte lineage during the different stages of myelination and its involvement on oligodendrocyte maturation, branching, myelin-gene expression, myelination, and axonal function...
March 2018: Glia
https://www.readbyqxmd.com/read/29090003/structure-and-function-of-the-contactin-associated-protein-family-in-myelinated-axons-and-their-relationship-with-nerve-diseases
#15
REVIEW
Yan Zou, Wei-Feng Zhang, Hai-Ying Liu, Xia Li, Xing Zhang, Xiao-Fang Ma, Yang Sun, Shi-Yi Jiang, Quan-Hong Ma, De-En Xu
The contactin-associated protein (Caspr) family participates in nerve excitation and conduction, and neurotransmitter release in myelinated axons. We analyzed the structures and functions of the Caspr family-CNTNAP1 (Caspr1), CNTNAP2 (Caspr2), CNTNAP3 (Caspr3), CNTNAP4 (Caspr4) and CNTNAP5 (Caspr5), Caspr1-5 is not only involved in the formation of myelinated axons, but also participates in maintaining the stability of adjacent connections. Caspr1 participates in the formation, differentiation, and proliferation of neurons and astrocytes, and in motor control and cognitive function...
September 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29089585/antibodies-against-peripheral-nerve-antigens-in-chronic-inflammatory-demyelinating-polyradiculoneuropathy
#16
Luis Querol, Ana M Siles, Roser Alba-Rovira, Agustín Jáuregui, Jérôme Devaux, Catherine Faivre-Sarrailh, Josefa Araque, Ricard Rojas-Garcia, Jordi Diaz-Manera, Elena Cortés-Vicente, Gisela Nogales-Gadea, Miquel Navas-Madroñal, Eduard Gallardo, Isabel Illa
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous disease in which diverse autoantibodies have been described but systematic screening has never been performed. Detection of CIDP-specific antibodies may be clinically useful. We developed a screening protocol to uncover novel reactivities in CIDP. Sixty-five CIDP patients and 28 controls were included in our study. Three patients (4.6%) had antibodies against neurofascin 155, four (6.2%) against contactin-1 and one (1.5%) against the contactin-1/contactin-associated protein-1 complex...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29075658/improving-the-antibody-based-evaluation-of-autoimmune-encephalitis
#17
Lindsey McCracken, Junxian Zhang, Maxwell Greene, Anne Crivaro, Joyce Gonzalez, Malek Kamoun, Eric Lancaster
OBJECTIVE: We tested whether antibody screening samples of patients with suspected autoimmune encephalitis with additional research assays would improve the detection of autoimmune encephalitis compared with standard clinical testing alone. METHODS: We examined 731 samples (333 CSF, 182 sera, and 108 pairs) from a cohort of 623 patients who were tested for CNS autoantibodies by the University of Pennsylvania clinical laboratory over a 24-month period with cell-based assays (CBAs) on commercially obtained slides of fixed cells for antibodies to NMDA receptor (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), γ-aminobutyric acid-B receptor (GABAB R), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (Caspr2), and glutamic acid decarboxylase (GAD65)...
November 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/29055902/lgi1-caspr2-and-related-antibodies-a-molecular-evolution-of-the-phenotypes
#18
REVIEW
Sophie N M Binks, Christopher J Klein, Patrick Waters, Sean J Pittock, Sarosh R Irani
Recent biochemical observations have helped redefine antigenic components within the voltage-gated potassium channel (VGKC) complex. The related autoantibodies may be now divided into likely pathogenic entities, which target the extracellular domains of leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2), and species that target intracellular neuronal components and are likely non-pathogenic. This distinction has enhanced clinical practice as direct determination of LGI1 and CASPR2 antibodies offers optimal sensitivity and specificity...
October 21, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28968899/cntnap4-impacts-epilepsy-through-gabaa-receptors-regulation-evidence-from-temporal-lobe-epilepsy-patients-and-mouse-models
#19
Yafei Shangguan, Xin Xu, Baigalimaa Ganbat, Yun Li, Wei Wang, Yong Yang, Xi Lu, Chao Du, Xin Tian, Xuefeng Wang
Epilepsy is a serious neurological condition characterized by recurrent unprovoked seizures. The exact etiology of epilepsy is not fully understood. Here, we demonstrated that the expression of contactin-associated protein-like 4 (CNTNAP4) was decreased in the temporal neocortex of epileptic patients and in the hippocampus and cortex of epileptic mice. Lentivirus-mediated knock-down of CNTNAP4 in the hippocampus increased mice susceptibility to epilepsy. Conversely, lentivirus-mediated overexpression of CNTNAP4 decreased epileptic behavior in mice...
August 22, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28966979/developmental-disruption-of-gabaar-meditated-inhibition-in-cntnap2-ko-mice
#20
Morgan S Bridi, Su Mi Park, Shiyong Huang
GABA released from presynaptic sites induces short-lived phasic inhibition mediated by synaptic GABAA receptors (GABAARs) and longer-duration tonic inhibition mediated by extrasynaptic GABAA or GABAB receptors (GABABRs). A number of studies have found that contactin-associated protein 2 (Cntnap2) knockout (KO) mice, a well-established mouse model of autism, exhibit reduced interneuron numbers and aberrant phasic inhibition. However, little is known about whether tonic inhibition is disrupted in Cntnap2 KO mice and when the disruption of inhibition begins to occur during postnatal development...
September 2017: ENeuro
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