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https://www.readbyqxmd.com/read/29034113/low-neurotoxicity-of-onx-0914-supports-the-idea-of-specific-immunoproteasome-inhibition-as-a-side-effect-limiting-therapeutic-strategy
#1
Laura von Brzezinski, Paula Säring, Peter Landgraf, Clemens Cammann, Ulrike Seifert, Daniela C Dieterich
Application of the proteasome inhibitor Bortezomib for the treatment of haematopoietic malignancies such as multiple myeloma significantly improves the average overall survival of patients. However, one of the most severe side effects is the development of peripheral neuropathies caused by neurotoxic effects of Bortezomib limiting its therapeutic efficacy. With ONX-0914 a specific inhibitor of the β5i (LMP7)-immunosubunit containing proteasomes was developed that targets exclusively the proteasome subtypes mainly expressed in immune cells including B lymphocytes as the origin of multiple myeloma...
September 2017: European Journal of Microbiology & Immunology
https://www.readbyqxmd.com/read/28987189/diseases-of-the-peripheral-nerves
#2
Istvan Katona, Joachim Weis
This chapter reviews the diseases of the peripheral nerves from a neuropathologic point of view, with a special focus on specific morphologic changes, and includes a summary of the histopathologic methods available for their diagnosis. As the rate of obesity and the prevalence of type 2 diabetes increase, diabetic neuropathy is the most common cause of peripheral neuropathy. Many systemic disorders with metabolic origin, like amyloidosis, hepatic failure, vitamin deficiencies, uremia, lipid metabolism disorders, and others, can also cause axonal or myelin alterations in the peripheral nervous system...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28968369/sensory-polyneuropathies
#3
Kelly Graham Gwathmey
PURPOSE OF REVIEW: This article describes the methods of diagnosis and management of the sensory-predominant polyneuropathies. To simplify the approach to this category of patients, sensory-predominant polyneuropathies are divided broadly into either small fiber (or pain-predominant) neuropathies and large fiber (or ataxia-predominant) neuropathies, of which the sensory neuronopathies (dorsal root ganglionopathies) are highlighted. RECENT FINDINGS: Physicians can now easily perform skin biopsies in their offices, allowing access to the gold standard pathologic diagnostic tool for small fiber neuropathies...
October 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/28954337/-clinical-analysis-of-paraneoplastic-neurological-syndrome-associated-with-thymoma
#4
H S Liu, H T Ren, L X Zhou, S Q Li, B Peng, L Y Cui, H Z Guan
Objectives: To investigate the clinical features, diagnosis and treatment of antibody mediated paraneoplastic neurological syndrome associated with thymoma. Methods: From 2012 to 2017, the paraneoplastic antibody and neuron antibody were tested from both blood and cerebrospinal fluid (CSF) in consecutive patients clinically suspected with neurological paraneoplastic syndromes/unknown encephalitis in Peking Union Medical College Hospital.The clinical data, lab results, electrophysiological examinations, imaging features, treatment and clinical prognosis were collected...
September 19, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28948076/peripheral-neuropathy-in-limbic-encephalitis-with-anti-glutamate-receptor-antibodies-case-report-and-systematic-literature-review
#5
Yi-Chia Wei, Chin-Chang Huang, Chi-Hung Liu, Hung-Chou Kuo, Jainn-Jim Lin
INTRODUCTION: Autoantibodies to the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and N-methyl-d-aspartate (NMDA) receptor are known to be the causes of autoimmune encephalitis particularly limbic encephalitis. The involvement of the peripheral nervous system is rarely reported. METHODS: We analyzed the serial nerve conduction studies of a previously reported case of anti-AMPA receptor encephalitis, who was presented with conscious disturbance and quadriplegia...
September 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28936613/chronic-inflammatory-demyelinating-polyradiculoneuropathy-and-anesthesia-a-case-series
#6
Andrew R Mortenson, Juraj Sprung, James C Watson, P James B Dyck, Toby N Weingarten
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired autoimmune demyelinating polyneuropathy characterized by symmetrical diffuse weakness that also can rarely affect bulbar and respiratory muscles. The study objective was to describe perioperative outcomes of patients with CIDP who received general anesthesia. This retrospective observational study evaluated patients with active (diagnosed or treated within the previous year) CIDP who underwent general anesthesia at our institution between January 1, 2010, and December 31, 2015...
September 21, 2017: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/28927011/assessing-autophagy-in-sciatic-nerves-of-a-rat-model-that-develops-inflammatory-autoimmune-peripheral-neuropathies
#7
REVIEW
Susana Brun, Nicolas Schall, Hélène Jeltsch-David, Jérôme de Sèze, Sylviane Muller
The rat sciatic nerve has attracted widespread attention as an excellent model system for studying autophagy alterations in peripheral neuropathies. In our laboratory, we have developed an original rat model, which we used currently in routine novel drug screening and to evaluate treatment strategies for chronic inflammatory demyelinating polyneuropathy (CIDP) and other closely related diseases. Lewis rats injected with the S-palmitoylated P0(180-199) peptide develop a chronic, sometimes relapsing-remitting type of disease...
September 18, 2017: Cells
https://www.readbyqxmd.com/read/28926640/aire-deficient-mice-provide-a-model-of-corneal-and-lacrimal-gland-neuropathy-in-sj%C3%A3-gren-s-syndrome
#8
Feeling Y Chen, Albert Lee, Shaokui Ge, Sara Nathan, Sarah M Knox, Nancy A McNamara
Sjögren's syndrome (SS) is a chronic, autoimmune exocrinopathy that leads to severe dryness of the mouth and eyes. Exocrine function is highly regulated by neuronal mechanisms but little is known about the link between chronic inflammation, innervation and altered exocrine function in the diseased eyes and exocrine glands of SS patients. To gain a better understanding of neuronal regulation in the immunopathogenesis of autoimmune exocrinopathy, we profiled a mouse model of spontaneous, autoimmune exocrinopathy that possess key characteristics of peripheral neuropathy experienced by SS patients...
2017: PloS One
https://www.readbyqxmd.com/read/28911826/immunoproteasome-selective-and-non-selective-inhibitors-a-promising-approach-for-the-treatment-of-multiple-myeloma
#9
REVIEW
Roberta Ettari, Maria Zappalà, Silvana Grasso, Caterina Musolino, Vanessa Innao, Alessandro Allegra
The ubiquitin-proteasome system (UPS) is the major non-lysosomal proteolytic system for the degradation of abnormal or damaged proteins no longer required. The proteasome is involved in degradation of numerous proteins which regulate the cell cycle, indicating a role in controlling cell proliferation and maintaining cell survival. Defects in the UPS can lead to anarchic cell proliferation and to tumor development. For these reasons UPS inhibition has become a significant new strategy for drug development in cancer treatment...
September 11, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28904462/clinical-spectrum-therapeutic-outcomes-and-prognostic-predictors-in-sjogren-s-syndrome-associated-neuropathy
#10
Ajith Sivadasan, Karthik Muthusamy, Bimal Patel, Rohit Ninan Benjamin, A T Prabhakar, Vivek Mathew, Sanjith Aaron, Mathew Alexander
OBJECTIVES: There are limited data regarding long-term follow-up and therapeutic outcomes in Sjogren's syndrome (SS)-associated peripheral neuropathy. In this study, we aim to study the clinical, electrophysiological spectrum and therapeutic responses among the different subtypes of SS-associated neuropathy. The predictors of suboptimal treatment response will be identified. METHODS: The study included a retrospective cohort of patients with SS-associated neuropathy between January 2012 and November 2015...
July 2017: Annals of Indian Academy of Neurology
https://www.readbyqxmd.com/read/28875858/managing-neuropathic-pain-in-multiple-sclerosis-pharmacological-interventions
#11
Samuel S Duffy, Justin G Lees, Chamini J Perera, Gila Moalem-Taylor
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Of the plethora of motor and sensory disturbances experienced by sufferers, neuropathic pain is a highly prevalent and debilitating symptom, and at present remains extremely difficult to treat. Common forms of neuropathic pain seen in MS patients include central neuropathic pain, Lhermitte's phenomenon and trigeminal neuralgia, which are all speculated to arise from specific patterns of lesion formation...
September 6, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28873125/neurological-complications-associated-with-anti-programmed-death-1-pd-1-antibodies
#12
Justin C Kao, Bing Liao, Svetomir N Markovic, Christopher J Klein, Elie Naddaf, Nathan P Staff, Teerin Liewluck, Julie E Hammack, Paola Sandroni, Heidi Finnes, Michelle L Mauermann
Importance: Neurological complications are an increasingly recognized consequence of the use of anti-programmed death 1 (PD-1) antibodies in the treatment of solid-organ tumors, with an estimated frequency of 4.2%. To date, the clinical spectrum and optimum treatment approach are not established. Objective: To investigate the frequency, clinical spectrum, and optimum treatment approach to neurological complications associated with anti-PD-1 therapy. Design, Setting, and Participants: This single-center, retrospective cohort study was conducted from either September or December 2014 (the approval dates of the study drugs by the US Food and Drug Administration) to May 19, 2016...
October 1, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28868890/autoimmunity-autonomic-neuropathy-and-the-hpv-vaccination-a-vulnerable-subpopulation
#13
Jill R Schofield, Jeanne E Hendrickson
No abstract text is available yet for this article.
September 1, 2017: Clinical Pediatrics
https://www.readbyqxmd.com/read/28854831/autoimmune-diseases-induced-by-biological-agents-a-review-of-12-731-cases-biogeas-registry
#14
Marta Pérez-De-Lis, Soledad Retamozo, Alejandra Flores-Chávez, Belchin Kostov, Roberto Perez-Alvarez, Pilar Brito-Zerón, Manuel Ramos-Casals
Biological drugs are therapies designed to target a specific molecule of the immune system that have been linked with the development of autoimmune diseases. Areas covered: The BIOGEAS Registry currently collects information about nearly 13,000 reported cases of autoimmune diseases developed in patients exposed to biologics, including more than 50 different systemic and organ-specific autoimmune disorders, of which psoriasis (n=6375), inflammatory bowel disease (n=845), demyelinating CNS disease (n=803), interstitial lung disease (n=519) and lupus (n=369) were the most frequently reported...
November 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28831691/parvovirus-b19-infection-associated-with-hemolytic-anemia-and-cranial-polyneuropathy
#15
João Sequeira, Ana Calado, Margarida Dias, Manuel Manita
Parvovirus B19 (PB19) is a common, widespread, small, single-stranded DNA virus which has been linked with a broad spectrum of clinical illnesses, including a variety of neurological complications such as encephalitis, meningitis, myelitis, stroke, cerebellar ataxia, and neuropathy. The authors describe a case of PB19 infection associated with hemolytic anemia and cranial polyneuropathy involving the second and third cranial nerves in a 23-year-old immunocompetent woman. The diagnosis of acute PB19 infection was established with detection of positive DNA and anti-PB19 IgM antibodies in blood samples...
August 22, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28827487/clinical-and-laboratory-profiles-of-idiopathic-small-fiber-neuropathy-in-children-case-series
#16
Jafar Kafaie, Ali Al Balushi, Minsoo Kim, Alan Pestronk
The role of autoimmune mechanisms in idiopathic small fiber neuropathy (SFN) is not completely understood. Serum IgM binding to trisulfated disaccharide IdoA2S-GlcNS-6S (TS-HDS) and IgG to fibroblast growth factor receptor 3 were associated with sensory motor polyneuropathies and sensory neuronopathy among others. In this retrospective case review, we describe the clinical and laboratory findings of idiopathic SFN in a small cohort of pediatric patients. Eight children were diagnosed with SFN clinically and confirmed by reduced epidermal nerve fiber density...
September 2017: Journal of Clinical Neuromuscular Disease
https://www.readbyqxmd.com/read/28819062/nodes-paranodes-and-neuropathies
#17
REVIEW
Janev Fehmi, Steven S Scherer, Hugh J Willison, Simon Rinaldi
This review summarises recent evidence supporting the involvement of the specialised nodal and perinodal domains (the paranode and juxtaparanode) of myelinated axons in the pathology of acquired, inflammatory, peripheral neuropathies.The identification of new target antigens in the inflammatory neuropathies heralds a revolution in diagnosis, and has already begun to inform increasingly targeted and individualised therapies. Rapid progress in our basic understanding of the highly specialised nodal regions of peripheral nerves serves to strengthen the links between their unique microstructural identities, functions and pathologies...
August 17, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28789710/transplanted-human-fecal-microbiota-enhanced-guillain-barr%C3%A3-syndrome-autoantibody-responses-after-campylobacter-jejuni-infection-in-c57bl-6-mice
#18
Phillip T Brooks, Kelsey A Brakel, Julia A Bell, Christopher E Bejcek, Trey Gilpin, Jean M Brudvig, Linda S Mansfield
BACKGROUND: Campylobacter jejuni is the leading antecedent infection to the autoimmune neuropathy Guillain-Barré syndrome (GBS), which is accompanied by an autoimmune anti-ganglioside antibody attack on peripheral nerves. Previously, we showed that contrasting immune responses mediate C. jejuni induced colitis and autoimmunity in interleukin-10 (IL-10)-deficient mice, dependent upon the infecting strain. Strains from colitis patients elicited T helper 1 (TH1)-dependent inflammatory responses while strains from GBS patients elicited TH2-dependent autoantibody production...
August 8, 2017: Microbiome
https://www.readbyqxmd.com/read/28741102/the-range-of-neurological-complications-in-chikungunya-fever
#19
T Cerny, M Schwarz, U Schwarz, J Lemant, P Gérardin, E Keller
BACKGROUND: Chikungunya fever is a globally spreading mosquito-borne disease that shows an unexpected neurovirulence. Even though the neurological complications have been a major cause of intensive care unit admission and death, to date, there is no systematic analysis of their spectrum available. OBJECTIVE: To review evidence of neurological manifestations in Chikungunya fever and map their epidemiology, clinical spectrum, pathomechanisms, diagnostics, therapies and outcomes...
May 25, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28736206/bpag1-in-muscles-structure-and-function-in-skeletal-cardiac-and-smooth-muscle
#20
REVIEW
Masao Horie, Nozomu Yoshioka, Hirohide Takebayashi
BPAG1, also known as Dystonin or BP230, belongs to the plakin family of proteins, which has multiple cytoskeleton-binding domains. Several BPAG1 isoforms are produced by a single BPAG1 genomic locus using different promoters and exons. For example, BPAG1a, BPAG1b, and BPAG1e are predominantly expressed in the nervous system, muscle, and skin, respectively. Among BPAG1 isoforms, BPAG1e is well studied because it was first identified as an autoantigen in patients with bullous pemphigoid, an autoimmune skin disease...
July 20, 2017: Seminars in Cell & Developmental Biology
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