scholarly journals Differential Binding of Autoantibodies to MOG Isoforms in Inflammatory Demyelinating Diseases

2021 ◽  
Vol 8 (5) ◽  
pp. e1027
Author(s):  
Kathrin Schanda ◽  
Patrick Peschl ◽  
Magdalena Lerch ◽  
Barbara Seebacher ◽  
Swantje Mindorf ◽  
...  

ObjectiveTo analyze serum immunoglobulin G (IgG) antibodies to major isoforms of myelin oligodendrocyte glycoprotein (MOG-alpha 1-3 and beta 1-3) in patients with inflammatory demyelinating diseases.MethodsRetrospective case-control study using 378 serum samples from patients with multiple sclerosis (MS), patients with non-MS demyelinating disease, and healthy controls with MOG alpha-1-IgG positive (n = 202) or negative serostatus (n = 176). Samples were analyzed for their reactivity to human, mouse, and rat MOG isoforms with and without mutations in the extracellular MOG Ig domain (MOG-ecIgD), soluble MOG-ecIgD, and myelin from multiple species using live cell-based, tissue immunofluorescence assays and ELISA.ResultsThe strongest IgG reactivities were directed against the longest MOG isoforms alpha-1 (the currently used standard test for MOG-IgG) and beta-1, whereas the other isoforms were less frequently recognized. Using principal component analysis, we identified 3 different binding patterns associated with non-MS disease: (1) isolated reactivity to MOG-alpha-1/beta-1 (n = 73), (2) binding to MOG-alpha-1/beta-1 and at least one other alpha, but no beta isoform (n = 64), and (3) reactivity to all 6 MOG isoforms (n = 65). The remaining samples were negative (n = 176) for MOG-IgG. These MOG isoform binding patterns were associated with a non-MS demyelinating disease, but there were no differences in clinical phenotypes or disease course. The 3 MOG isoform patterns had distinct immunologic characteristics such as differential binding to soluble MOG-ecIgD, sensitivity to MOG mutations, and binding to human MOG in ELISA.ConclusionsThe novel finding of differential MOG isoform binding patterns could inform future studies on the refinement of MOG-IgG assays and the pathophysiologic role of MOG-IgG.

2021 ◽  
Author(s):  
Yuhang Yang ◽  
Qian Yang ◽  
Yinsheng Zhang ◽  
Chaohui Lian ◽  
Honghui He ◽  
...  

AbstractBackgroundAdvances in mass spectrometry are providing new insights into the role of metabolomics in the aetiology of many diseases. Studies in retinopathy of prematurity (ROP), for instance, overlooked the role of metabolic alterations in disease development. Here, we employed comprehensive metabolic profiling and gold-standard metabolic analysis to explore major metabolites and metabolic pathways significantly affected in early stages of pathogenesis toward ROP.MethodsThis is a multicentre, retrospective case-control study. We collected serums from 57 ROP cases and 57 strictly baseline matched non-ROP controls. Non-targeted ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) from Metabolon, Inc. was used to detect the metabolites in serum samples. Machine learning was used to unravel most affected metabolites and pathways in ROP development.ResultsCompared to non-ROP controls, we found a significant metabolic perturbation in the ROP serums, featured with an increase in lipid, nucleotide, carbohydrate metabolites and a lower level of peptides. Machine leaning helped to distinguish a cluster of metabolic pathways (glycometabolism, redox homeostasis, lipid metabolism and arginine pathway) that were strongly related to the development of ROP. In addition, we found that the severity of ROP was related to the level of creatinine and ribitol.ConclusionIn the current study, our results suggested a strong link between metabolic profiling and retinal neovascularization during ROP pathogenesis. These findings provided an insight into identifying novel metabolic biomarkers for ROP diagnosis and prevention.


2021 ◽  
Author(s):  
Yan Chen ◽  
Ying Jia ◽  
Rui Zhang ◽  
Qiuju Wang ◽  
Tingwenli Huang ◽  
...  

Abstract Imatinib mesylate (IM) is highly efficacious in the treatment of gastrointestinal stromal tumors (GISTs). Therapeutic drug monitoring (TDM) and pharmacogenetic screening are affirmed for better management of IM therapy. The goal of this study was to explore the most sensitive metabolites and the role of organic cation transporter 1 (OCT1) on single nuclear polymorphisms (SNP) of IM treatment, which could supply a greater mechanistic understanding of therapeutic effect or resistance of IM. A total of 40 human serum samples from patients with GISTs were collected for TDM. Basing on the results of TDM, the untargeted metabolomic analysis was to determine characteristics of the serum. Principal component analysis (PCA), orthogonal partial least-squares discrimination analysis (OPLS-DA), and heat map were used for multivariate analysis. In addition, KEGG database were used to identify the pathways of metabolites. Differential metabolites were identified based on a heat map with a t-test threshold (p < 0.05), fold-change (FC) threshold (FC > 1.5 or FC < 2/3) and variable importance (VIP) in the projection (VIP>1). The potential differential metabolites were included D-sphingosine, 1-sphingosine phosphate, phytosphingosine and phosphoethanolamine, which were belonged to the metabolism pathway of sphingolipid. Because of the function of OCT1 transporters was related with drug in the liver, the OCT1 1386C>A (rs 622342) was statistically significant (P<0.05) with IM plasma concentration. Thus, this study demonstrated that sphingolipid metabolism should be considered as the potential pathway of IM treated GISTs, which could bring us a clue to new mechanism for IM treatment of patients with GISTs.


2019 ◽  
Author(s):  
F Foerster ◽  
K Mönkemüller ◽  
PR Galle ◽  
H Neumann

Author(s):  
Vinod Kumar ◽  
Bhupen Songra ◽  
Richa Jain ◽  
Deeksha Mehta

Background: the present study was under taken to determine the role of CA-125 in the diagnosis of acute appendicitis (AA), to prevent its complications and also in preventing negative appendicectomies in tertiary care hospital. Methods: The study was conducted at a tertiary care and research center between 01/03/2018 to 30/06/2019. Patients admitted to the surgery department with diagnosis of AA were considered for the study. After informed consent, a, standardized history was obtained as a case Performa. Serum samples from all the cases with clinical diagnosis of AA were obtained and stored. Only the cases with histopathologically approved AA were included in the study. Cases operated for clinical diagnosis of AA, but not histopathologically proven AA was not included in the study. CA125 levels in cases with definitive diagnosis of AA were measured. Results: In present study, ROC curve analysis revealed the sensitivity of 87.27 % and specificity of 90.91 % when the CA 125 cut-off value of > 16.8 was taken to diagnose acute appendicitis. AUC was 0.911 with a standard error of 0.0292. Conclusion: In this study we have observed that CA125 showed a positive correlation with acute appendicitis, that was statistically not significant (P>0.05). We didn’t evaluate the correlation with the disease severity. We consider that CA125 can be used as a marker in acute appendicitis cases although further research is still needed. Keywords: CA125, Acute Appendicitis, Surgery.


Author(s):  
Vike Martina Plock

This chapter analyzes the role of fashion as a discursive force in Rosamond Lehmann’s 1932 coming-of-age novel Invitation to the Waltz. Reading the novel alongside such fashion magazines as Vogue, it demonstrates Lehmann’s awareness that 1920s fashion, in spite of its carefully stylized public image as harbinger of originality, emphasized the importance of following preconceived (dress) patterns in the successful construction of modern feminine types. Invitation to the Waltz, it argues, opposes the production of patterned types and celebrates difference and disobedience in its stead. At the same time, the novel’s formal appearance is nonetheless dependent on the very same tenets it criticizes. On closer scrutiny, it is seen to reveal its resemblance to Virginia Woolf’s To the Lighthouse (1927). A tension between imitation and originality determines sartorial fashion choices. This chapter shows that female authorship in the inter-war period was subjected to the same market forces that controlled and sustained the organization of the fashion industry.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 977-982
Author(s):  
Mohamed J. Saadh ◽  
Bashar Haj Rashid M ◽  
Roa’a Matar ◽  
Sajeda Riyad Aldibs ◽  
Hala Sbaih ◽  
...  

SARS-COV2 virus causes Coronavirus disease (COVID-19) and represents the causative agent of a potentially fatal disease that is of great global public health concern. The novel coronavirus (2019) was discovered in 2019 in Wuhan, the market of the wet animal, China with viral pneumonia cases and is life-threatening. Today, WHO announces COVID-19 outbreak as a pandemic. COVID-19 is likely to be zoonotic. It is transmitted from bats as intermediary animals to human. Also, the virus is transmitted from human to human who is in close contact with others. The computerized tomographic chest scan is usually abnormal even in those with no symptoms or mild disease. Treatment is nearly supportive; the role of antiviral agents is yet to be established. The SARS-COV2 virus spreads faster than its two ancestors, the SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), but has lower fatality. In this article, we aimed to summarize the transmission, symptoms, pathogenesis, diagnosis, treatment, and vaccine to control the spread of this fatal disease.


2020 ◽  
Vol 2 (3) ◽  
pp. 19-23
Author(s):  
Shakhlo Botirova ◽  
Keyword(s):  

In this article , in the novel “Rebellion and obedience” by Ulugbek Hamdam, the author analyzes the artistic psychological description of a person on the path of development in the center of an integral complex metaphorical system of being. The novel “Rebellion and obedience” is based onthe method of metaphorization of reality. In it, a personexperiences vertigo about who he is and what powerful being he possesses. The reason for this is a riot. After much agony, he obeys. Allegedly thus proves its existence. Finds answers to certain riddles


Author(s):  
Larisa Botnari

Although very famous, some key moments of the novel In Search of Lost Time, such as those of the madeleine or the uneven pavement, often remain enigmatic for the reader. Our article attempts to formulate a possible philosophical interpretation of the narrator's experiences during these scenes, through a confrontation of the Proustian text with the ideas found in the System of Transcendental Idealism (1800) of the German philosopher F. W. J. Schelling. We thus try to highlight the essential role of the self in Marcel Proust's aesthetic thinking, by showing that the mysterious happiness felt by the narrator, and from which the project of creating a work of art is ultimately born, is similar to the experiences of pure self-consciousness evoked and analyzed by Schellingian philosophy of art.


2020 ◽  
Author(s):  
Agnieszka Wykowska ◽  
Jairo Pérez-Osorio ◽  
Stefan Kopp

This booklet is a collection of the position statements accepted for the HRI’20 conference workshop “Social Cognition for HRI: Exploring the relationship between mindreading and social attunement in human-robot interaction” (Wykowska, Perez-Osorio &amp; Kopp, 2020). Unfortunately, due to the rapid unfolding of the novel coronavirus at the beginning of the present year, the conference and consequently our workshop, were canceled. On the light of these events, we decided to put together the positions statements accepted for the workshop. The contributions collected in these pages highlight the role of attribution of mental states to artificial agents in human-robot interaction, and precisely the quality and presence of social attunement mechanisms that are known to make human interaction smooth, efficient, and robust. These papers also accentuate the importance of the multidisciplinary approach to advance the understanding of the factors and the consequences of social interactions with artificial agents.


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