- Multiple Sclerosis Research Studies
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cytokine Signaling Pathways and Interactions
- Systemic Lupus Erythematosus Research
- Immune Response and Inflammation
- Cell Adhesion Molecules Research
- RNA regulation and disease
- Monoclonal and Polyclonal Antibodies Research
- Peripheral Neuropathies and Disorders
- Immune Cell Function and Interaction
- Nerve injury and regeneration
- Heat shock proteins research
- Barrier Structure and Function Studies
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Axon Guidance and Neuronal Signaling
- Virology and Viral Diseases
- Systemic Sclerosis and Related Diseases
- Neuroscience and Neuropharmacology Research
- Polyomavirus and related diseases
- Immune responses and vaccinations
- Prion Diseases and Protein Misfolding
The Bronx Defenders
1987-2023
Albert Einstein College of Medicine
2010-2021
University of Missouri–St. Louis
2021
Columbus Oncology and Hematology Associates
2010-2017
Montefiore Medical Center
2017
New York Proton Center
1994-2010
John F. Kennedy Center for the Performing Arts
1989-2009
Yeshiva University
1993-2009
Society for Neuroscience
2007-2009
Medical University of Lodz
1995-2007
Abstract Recombinant human tumor necrosis factor (rhTNF) has been tested for its effect on myelinated cultures of mouse spinal cord tissue. As controls, recombinant interferon gamma (rhIFN) and interleukin‐2 (rhIL‐2) were tested, as well T‐cell supernatants, antigalactocerebroside serum, normal culture medium. It was found that rhTNF induced delayed‐onset (18–24 hr) oligodendrocyte a type myelin dilatation peculiar to this system. Some nerve fibers progressed demyelination by 72 hours. The...
The expression of the adhesion molecules, vascular cell molecule-1 (VCAM-1) and intercellular (ICAM-1), their respective receptors on leukocytes, very late activation antigen-4 (VLA-4) lymphocyte function-associated antigen-1 (LFA-1), together with a selection proinflammatory immunomodulatory cytokines (interleukin [IL]-1, IL-2, IL-4, IL-10, tumor necrosis factor-alpha [TNF-alpha], transforming growth factor-beta [TGF-beta], interferon-gamma [IFN-gamma] was examined by immunocytochemistry in...
Multiple sclerosis (MS) brain tissue, spleen, and PBMC were studied using immunocytochemistry FACS for immunoreactivity lymphotoxin (LT) TNF. Both cytokines identified in acute chronic active MS lesions but absent from silent lesions. LT was associated with CD3+ lymphocytes Leu-M5+ microglia cells at the lesion edge to a lesser extent, adjacent white matter. TNF astrocytes all areas of lesion, foamy macrophages center lesion. In lesions, endothelial noted edge. No or reactivity detected...
The properties and outcome of an immune response are best predicted by the lymphokine phenotype responding T cells. Cytokines produced CD4+ helper type 1 (Th1) cells mediate delayed hypersensitivity (DTH) inflammatory responses, whereas cytokines Th2 cell functions for antibody production. To determine whether induction Th2-like would modulate response, interleukin 4 (IL-4) was administered to animals with experimental allergic encephalomyelitis (EAE), a prototypic autoimmune disease...
The effect of cytokines on astrocytes cultured from mature bovine brain was determined both in a serum-containing medium and chemically-defined medium. results showed that serum-free medium, human TNF and, to lesser degree, IL-6 lymphotoxin, were mitogenic for astrocytes. Increased uptake [3H]thymidine could be detected within 36 h vitro its presence confirmed by autoradiography. In contrast, neither IL-1 alpha nor beta induced astrocyte proliferation but some synergistic with serum after 72...
Encounters with antigen can stimulate T cells to become activated and proliferate, nonresponsive antigen, or die. cell death was shown be a physiological response interleukin-2-stimulated cycling receptor reengagement at high doses. This feedback regulatory mechanism attenuates the immune by deleting portion of newly dividing, antigen-reactive cells. deleted autoreactive abrogated clinical pathological signs autoimmune encephalomyelitis in mice after repetitive administration myelin basic protein.
Adrenoleukodystrophy was diagnosed pathologically in 17 male patients. The diagnosis suggested by clinical and laboratory signs of primary adrenal failure neurological referable to the degeneration white matter. Neurological findings usually predominated over stigmata failure. Adrenal biopsy has proved be most reliable diagnostic test, while brain often been misleading. histological picture lesion differs substantially from that adrenal, but presence similar ultrastructural cytoplasmic...
Abstract Glutamate excitotoxicity, recently demonstrated in an animal model of multiple sclerosis (MS), is evoked by altered glutamate homeostasis. In the present study, we investigated major regulating factors excitotoxicity immunohistochemistry MS and control white matter with markers for production (glutaminase), transport (GLAST, GLT‐1 EAAT‐1), metabolism (glutamate dehydrogenase [GDH] glutamine synthetase [GS]), axonal damage (SMI 32) CNS cell types. Active lesions showed high‐level...
Abstract The cytotoxic effect of recombinant human cytokines was tested on glial cells cultured from mature bovine brain. Lymphotoxin (LT) and TNF induced injury to oligodendrocytes in a time dose-dependent fashion. other tested, IFN-gamma, IL-6, IL-2, did not affect culture over 72-h observation period. None the injured astrocytes same source. LT showed much more potent cytotoxicity than toward oligodendrocytes; changes were noted earlier (24 h) at lower units activity. Morphologic studies...
Encephalitogenic T cells that mediate experimental autoimmune encephalomyelitis (EAE) are commonly assumed to be exclusively CD4+, but formal proof is still lacking. In this study, we report synthetic peptides 35-55 from myelin oligodendrocyte glycoprotein (pMOG(35-55)) consistently activate a high proportion of CD8+ alphabetaTCR+ encephalitogenic in C57BL/6 (B6) mice. The potential MOG-specific was established by adoptive transfer CD8-enriched cells. These induced much more severe and...
Abstract To define a role for the cytokine tumor necrosis factor (TNF) in immune‐mediated demyelination, effect of anti‐TNF antibody was investigated with form experimental autoimmune encephalomyelitis (EAE) SJL/J mice induced by adoptive transfer myelin basic protein‐(MBP)‐sensitized T lymphocytes, an animal model human disease multiple sclerosis (MS). In three separate experiments, no mouse sensitized EAE and then treated intraperitoneal injection developed signs central nervous system...
Chronic inflammatory autoimmune diseases such as multiple sclerosis, diabetes, and rheumatoid arthritis are caused by CD4+ Th1 cells. Because Th2 cells antagonize cell functions in several ways, it is believed that immune deviation towards can prevent or cure diseases. Experimental encephalomyelitis (EAE) a demyelinating disease used model for sclerosis. Using an adoptive transfer system we assessed the role of EAE. In vitro generated from myelin basic protein (MBP)-specific TCR transgenic...
The distribution of T cells and cell subsets was examined within the human central nervous system in active lesions from seven patients with chronic multiple sclerosis. monoclonal antibodies anti-T11, anti-T4, anti-T8 were used to detect total (whole) cells, helper suppressor-cytotoxic respectively, a antibody against Ia for macrophages B cells. Lesion progression associated large numbers T4+ at lesion margin these extended great distances into adjacent normal-appearing white matter. T8+...
Olig1 and Olig2 are closely related basic helix-loop-helix (bHLH) transcription factors that expressed in myelinating oligodendrocytes their progenitor cells the developing central nervous system (CNS). is necessary for specification of oligodendrocytes, but biological functions during oligodendrocyte lineage development poorly understood. We show here function mice required not to develop brain repair it. Specifically, we demonstrate a genetic requirement repairing types lesions occur...
Abstract Experimental allergic encephalomyelitis (EAE) is an autoimmune disease characterized by inflammation and demyelination in the central nervous system. The effect of immunosuppressive molecule transforming growth factor-beta, (TGF-beta 1) on chronic relapsing EAE produced transfer myelin basic protein-specific T cell lines was studied. TGF-beta 1 markedly inhibited activation proliferation myelin-basic lymph node cells vitro. This reduced capacity these to EAE. In addition,...
Abstract Magnetic resonance imaging is a highly sensitive method for the detection of lesions multiple sclerosis and renders possible study evolution early lesions. Previous reports on magnetic following gandolinium‐diethylenetriamine pentaacetic acid (Gd‐DTPA) injection demonstrated that new can be recognized by contrast enhancement. The pathological basis these observations uncertain. We have had opportunity to at autopsy brain patient with chronic progressive who suffered acute worsening...
The renin-angiotensin-aldosterone system (RAAS) is a major regulator of blood pressure. octapeptide angiotensin II (AII) proteolytically processed from the decapeptide AI by angiotensin-converting enzyme (ACE), and then acts via type 1 2 receptors (AT1R AT2R). Inhibitors ACE antagonists AT1R are used in treatment hypertension, myocardial infarction, stroke. We now show that RAAS also plays role autoimmunity, exemplified multiple sclerosis (MS) its animal model, experimental autoimmune...