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Article ; Online: Editor's Note: Transitions at the JNEN.

Sobel, Raymond A

Journal of neuropathology and experimental neurology

2017 Volume 76, Issue 5, Page(s) 336

MeSH term(s)	Editorial Policies ; Humans ; Publishing
Language	English
Publishing date	2017-04-18
Publishing country	England
Document type	Editorial
ZDB-ID	3088-0
ISSN	1554-6578 ; 0022-3069
ISSN (online)	1554-6578
ISSN	0022-3069
DOI	10.1093/jnen/nlx019
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Article ; Online: Investigation into Cardiac Myhc-α 334-352-Specific TCR Transgenic Mice Reveals a Role for Cytotoxic CD4 T Cells in the Development of Cardiac Autoimmunity.

Sur, Meghna / Rasquinha, Mahima T / Mone, Kiruthiga / Massilamany, Chandirasegaran / Lasrado, Ninaad / Gurumurthy, Channabasavaiah / Sobel, Raymond A / Reddy, Jay

Cells

2024 Volume 13, Issue 3

Abstract: Myocarditis is one of the major causes of heart failure in children and young adults and can lead to dilated cardiomyopathy. Lymphocytic myocarditis could result from autoreactive ... ...

Abstract	Myocarditis is one of the major causes of heart failure in children and young adults and can lead to dilated cardiomyopathy. Lymphocytic myocarditis could result from autoreactive CD4
MeSH term(s)	Animals ; Humans ; Mice ; Autoimmunity ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes/pathology ; Mice, Inbred C57BL ; Mice, Transgenic ; Myocarditis ; Myosin Heavy Chains/genetics ; Receptors, Antigen, T-Cell ; T-Lymphocytes, Cytotoxic
Chemical Substances	Myh6 protein, mouse ; Myosin Heavy Chains (EC 3.6.4.1) ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2024-01-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13030234
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Article ; Online: Azetidine-2-Carboxylic Acid-Induced Oligodendrogliopathy: Relevance to the Pathogenesis of Multiple Sclerosis.

Sobel, Raymond A / Albertelli, Megan / Hinojoza, Julian R / Eaton, Mary Jane / Grimes, Kevin V / Rubenstein, Edward

Journal of neuropathology and experimental neurology

2022 Volume 81, Issue 6, Page(s) 414–433

Abstract: The naturally occurring imino acid azetidine-2-carboxylic acid (Aze) is consumed by humans and can be misincorporated in place of proline in myelin basic protein (MBP) in vitro. To determine Aze effects on the mammalian CNS in vivo, adult CD1 mice were ... ...

Abstract	The naturally occurring imino acid azetidine-2-carboxylic acid (Aze) is consumed by humans and can be misincorporated in place of proline in myelin basic protein (MBP) in vitro. To determine Aze effects on the mammalian CNS in vivo, adult CD1 mice were given Aze orally or intraperitoneally. Clinical signs reminiscent of MBP-mutant mice occurred with 600 mg/kg Aze exposure. Aze induced oligodendrocyte (OL) nucleomegaly and nucleoplasm clearing, dilated endoplasmic reticulum, cytoplasmic vacuolation, abnormal mitochondria, and Aze dose-dependent apoptosis. Immunohistochemistry demonstrated myelin blistering and nuclear translocation of unfolded protein response (UPR)/proinflammatory molecules (ATF3, ATF4, ATF6, eIF2α, GADD153, NFκB, PERK, XBP1), MHC I expression, and MBP cytoplasmic aggregation in OL. There were scattered microglial nodules in CNS white matter (WM); other CNS cells appeared unaffected. Mice given Aze in utero and postnatally showed more marked effects than their dams. These OL, myelin, and microglial alterations are found in normal-appearing WM (NAWM) in multiple sclerosis (MS) patients. Thus, Aze induces a distinct oligodendrogliopathy in mice that recapitulates MS NAWM pathology without leukocyte infiltration. Because myelin proteins are relatively stable throughout life, we hypothesize that Aze misincorporation in myelin proteins during myelinogenesis in humans results in a progressive UPR that may be a primary process in MS pathogenesis.
MeSH term(s)	Animals ; Azetidinecarboxylic Acid/chemistry ; Azetidinecarboxylic Acid/pharmacology ; Humans ; Mammals ; Mice ; Multiple Sclerosis/chemically induced ; Multiple Sclerosis/pathology ; Myelin Basic Protein ; Myelin Sheath/pathology ; Oligodendroglia/pathology ; Proline/chemistry
Chemical Substances	Myelin Basic Protein ; Azetidinecarboxylic Acid (5GZ3E0L9ZU) ; Proline (9DLQ4CIU6V)
Language	English
Publishing date	2022-05-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3088-0
ISSN	1554-6578 ; 0022-3069
ISSN (online)	1554-6578
ISSN	0022-3069
DOI	10.1093/jnen/nlac028
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Article ; Online: Evidence of increased sequestration of pro-resolving lipid mediators within brain esterified lipid pools of multiple sclerosis patients.

Shen, Qing / Otoki, Yurika / Sobel, Raymond A / Nagra, Rashed M / Taha, Ameer Y

Multiple sclerosis and related disorders

2022 Volume 68, Page(s) 104236

Abstract: Background: Unresolved inflammation in multiple sclerosis (MS) is associated with progressive demyelination and symptom worsening. In the brain, both inflammation and resolution pathways are mediated by free lipid mediators (i.e., oxylipins) that can be ...

Abstract	Background: Unresolved inflammation in multiple sclerosis (MS) is associated with progressive demyelination and symptom worsening. In the brain, both inflammation and resolution pathways are mediated by free lipid mediators (i.e., oxylipins) that can be derived from the enzymatic hydrolysis of esterified oxylipins . It is not known whether disturbances in the turnover of free lipid mediators from esterified pools exist in postmortem brain of MS patients. We hypothesized that resolution pathways are impaired in MS patients because of disturbances in the turnover of free pro-resolving lipid mediators from esterified lipids. The objective was to characterize free and esterified oxylipins in postmortem prefrontal cortex of MS and unaffected control participants. Methods: Oxylipins in free, neutral lipid and phospholipid pools were extracted from prefrontal cortex of 10 MS participants and 5 unaffected controls, separated by solid phase extraction columns, and quantified by ultra-high-pressure liquid chromatography-tandem mass spectrometry. Significant differences between the control and MS groups were determined by an unpaired t-test with Benjamini and Hochberg False Discovery Rate correction (10%) applied to oxylipins within each lipid pool. Results: The concentration of 7 esterified pro-resolving fatty acid epoxides within neutral lipids were significantly higher by 126%-285% in postmortem prefrontal cortex of MS compared to control participants. The concentration of esterified linoleic acid-derived 9(10)-epoxy-octadecenoic acid, a pro-inflammatory epoxide, was higher by 206% in MS compared to controls. No significant changes were observed in free or phospholipid-bound oxylipins. Conclusion: In MS, several pro-resolving lipid mediators are trapped within prefrontal cortex neutral lipids, potentially limiting their supply and availability in the free bioactive form. This may explain why inflammation resolution is impaired in MS patients.
Language	English
Publishing date	2022-10-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2022.104236
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Article ; Online: Lysia K.S. Forno, MD February 14, 1918-May 8, 2015.

Herrick, Maie K / Sobel, Raymond A

Journal of neuropathology and experimental neurology

2016 Volume 74, Issue 12, Page(s) 1180–1182

MeSH term(s)	Aged, 80 and over ; Biomedical Research/history ; Female ; History, 20th Century ; History, 21st Century ; Humans ; Neurodegenerative Diseases/history ; Neurodegenerative Diseases/pathology ; Neuropathology/history
Language	English
Publishing date	2016-02-22
Publishing country	England
Document type	Biography ; Historical Article ; Journal Article ; Portrait
ZDB-ID	3088-0
ISSN	1554-6578 ; 0022-3069
ISSN (online)	1554-6578
ISSN	0022-3069
DOI	10.1093/jnen/74.12.1180
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Article: A Monovalent Mt10-CVB3 Vaccine Prevents CVB4-Accelerated Type 1 Diabetes in NOD Mice.

Rasquinha, Mahima T / Lasrado, Ninaad / Sur, Meghna / Mone, Kiruthiga / Qiu, Haowen / Riethoven, Jean-Jack / Sobel, Raymond A / Reddy, Jay

Vaccines

2022 Volume 11, Issue 1

Abstract: Enteroviruses, which include Coxsackieviruses, are a common cause of virus infections in humans, and multiple serotypes of the group B Coxsackievirus (CVB) can induce similar diseases. No vaccines are currently available to prevent CVB infections because ...

Abstract	Enteroviruses, which include Coxsackieviruses, are a common cause of virus infections in humans, and multiple serotypes of the group B Coxsackievirus (CVB) can induce similar diseases. No vaccines are currently available to prevent CVB infections because developing serotype-specific vaccines is not practical. Thus, developing a vaccine that induces protective immune responses for multiple serotypes is desired. In that direction, we created a live-attenuated CVB3 vaccine virus, designated mutant (Mt)10, that offers protection against myocarditis and pancreatitis induced by CVB3 and CVB4 in disease-susceptible A/J mice. Here, we report that the Mt10 vaccine protected against CVB4-triggered type 1 diabetes (T1D) in non-obese diabetic (NOD) mice but the expected subsequent development of spontaneous T1D in these genetically predisposed NOD mice was not altered. We noted that Mt10 vaccine induced significant amounts of neutralizing antibodies, predominantly of the IgG2c isotype, and the virus was not detected in vaccine-challenged animals. Furthermore, monitoring blood glucose levels-and to a lesser extent, insulin antibodies-was found to be helpful in predicting vaccine responses. Taken together, our data suggest that the monovalent Mt10 vaccine has the potential to prevent infections caused by multiple CVB serotypes, as we have demonstrated in various pre-clinical models.
Language	English
Publishing date	2022-12-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11010076
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Article: A novel unifying hypothesis of multiple sclerosis.

Sobel, Raymond A

Journal of neuropathology and experimental neurology

2008 Volume 67, Issue 11, Page(s) 1032–1034

MeSH term(s)	Animals ; Azetidinecarboxylic Acid/adverse effects ; History, 19th Century ; Humans ; Models, Biological ; Multiple Sclerosis/etiology ; Multiple Sclerosis/history ; Multiple Sclerosis/pathology
Chemical Substances	Azetidinecarboxylic Acid (2517-04-6)
Language	English
Publishing date	2008-11
Publishing country	England
Document type	Comment ; Editorial ; Historical Article
ZDB-ID	3088-0
ISSN	1554-6578 ; 0022-3069
ISSN (online)	1554-6578
ISSN	0022-3069
DOI	10.1097/NEN.0b13e31818becal
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Article ; Online: CAR-T Cell-Mediated B-Cell Depletion in Central Nervous System Autoimmunity.

Gupta, Sasha / Simic, Milos / Sagan, Sharon A / Shepherd, Chanelle / Duecker, Jason / Sobel, Raymond A / Dandekar, Ravi / Wu, Gregory F / Wu, Wesley / Pak, John E / Hauser, Stephen L / Lim, Wendell / Wilson, Michael R / Zamvil, Scott S

Neurology(R) neuroimmunology & neuroinflammation

2023 Volume 10, Issue 2

Abstract: Background and objectives: Anti-CD20 monoclonal antibody (mAb) B-cell depletion is a remarkably successful multiple sclerosis (MS) treatment. Chimeric antigen receptor (CAR)-T cells, which target antigens in a non-major histocompatibility complex (MHC)- ... ...

Abstract	Background and objectives: Anti-CD20 monoclonal antibody (mAb) B-cell depletion is a remarkably successful multiple sclerosis (MS) treatment. Chimeric antigen receptor (CAR)-T cells, which target antigens in a non-major histocompatibility complex (MHC)-restricted manner, can penetrate tissues more thoroughly than mAbs. However, a previous study indicated that anti-CD19 CAR-T cells can paradoxically exacerbate experimental autoimmune encephalomyelitis (EAE) disease. We tested anti-CD19 CAR-T cells in a B-cell-dependent EAE model that is responsive to anti-CD20 B-cell depletion similar to the clinical benefit of anti-CD20 mAb treatment in MS. Methods: Anti-CD19 CAR-T cells or control cells that overexpressed green fluorescent protein were transferred into C57BL/6 mice pretreated with cyclophosphamide (Cy). Mice were immunized with recombinant human (rh) myelin oligodendrocyte protein (MOG), which causes EAE in a B-cell-dependent manner. Mice were evaluated for B-cell depletion, clinical and histologic signs of EAE, and immune modulation. Results: Clinical scores and lymphocyte infiltration were reduced in mice treated with either anti-CD19 CAR-T cells with Cy or control cells with Cy, but not with Cy alone. B-cell depletion was observed in peripheral lymphoid tissue and in the CNS of mice treated with anti-CD19 CAR-T cells with Cy pretreatment. Th1 or Th17 populations did not differ in anti-CD19 CAR-T cell, control cell-treated animals, or Cy alone. Discussion: In contrast to previous data showing that anti-CD19 CAR-T cell treatment exacerbated EAE, we observed that anti-CD19 CAR-T cells ameliorated EAE. In addition, anti-CD19 CAR-T cells thoroughly depleted B cells in peripheral tissues and in the CNS. However, the clinical benefit occurred independently of antigen specificity or B-cell depletion.
MeSH term(s)	Animals ; Humans ; Mice ; Antibodies, Monoclonal ; Antigens, CD19 ; Autoimmunity ; Central Nervous System ; Encephalomyelitis, Autoimmune, Experimental/drug therapy ; Mice, Inbred C57BL ; Multiple Sclerosis/drug therapy ; Myelin-Oligodendrocyte Glycoprotein ; T-Lymphocytes ; B-Lymphocytes ; Immunotherapy, Adoptive
Chemical Substances	Antibodies, Monoclonal ; Antigens, CD19 ; Myelin-Oligodendrocyte Glycoprotein
Language	English
Publishing date	2023-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2767740-0
ISSN	2332-7812 ; 2332-7812
ISSN (online)	2332-7812
ISSN	2332-7812
DOI	10.1212/NXI.0000000000200080
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Article: Neuropathology--for the living and the future.

Sobel, Raymond A

Journal of neuropathology and experimental neurology

2007 Volume 66, Issue 12, Page(s) 1057–1058

MeSH term(s)	History, 20th Century ; History, 21st Century ; Humans ; Nervous System Diseases/pathology ; Neurology/history ; Neurology/methods ; Neurology/trends ; Pathology/history ; Pathology/trends
Language	English
Publishing date	2007-12
Publishing country	England
Document type	Editorial ; Historical Article
ZDB-ID	3088-0
ISSN	1554-6578 ; 0022-3069
ISSN (online)	1554-6578
ISSN	0022-3069
DOI	10.1097/NEN.0b013e31815d8c10
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Article: Anti-viral T-cell immunity+anti-CNS autoantibody=a model for human acute disseminated encephalomyelitis or multiple sclerosis relapse?

Sobel, Raymond A

The American journal of pathology

2007 Volume 170, Issue 2, Page(s) 436–438

MeSH term(s)	Acute Disease ; Animals ; Autoimmune Diseases/genetics ; Autoimmune Diseases/immunology ; Autoimmune Diseases/pathology ; Autoimmune Diseases/virology ; Brain/immunology ; Brain/pathology ; Brain/virology ; Complement C3/deficiency ; Complement C3/immunology ; Encephalitis, Viral/genetics ; Encephalitis, Viral/immunology ; Encephalitis, Viral/pathology ; Encephalitis, Viral/virology ; Humans ; Mice ; Mice, Knockout ; Myelin Proteins ; Myelin-Associated Glycoprotein/immunology ; Myelin-Oligodendrocyte Glycoprotein ; Receptors, Fc/deficiency ; Receptors, Fc/immunology ; Spinal Cord/immunology ; Spinal Cord/pathology ; Spinal Cord/virology ; Transgenes/immunology
Chemical Substances	Complement C3 ; MOG protein, human ; Mog protein, mouse ; Myelin Proteins ; Myelin-Associated Glycoprotein ; Myelin-Oligodendrocyte Glycoprotein ; Receptors, Fc
Keywords	covid19
Language	English
Publishing date	2007-02
Publishing country	United States
Document type	Comment ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.2353/ajpath.2007.061098
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