Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paraneoplastic neurological syndromes (PNS) can be defined as remote effects of cancer that are not caused by the tumor and its metastasis, or by infection, ischemia or metabolic disruptions. PNS are rare, affecting less than 1/10,000 patients with cancer. Only the Lambert-Eaton myasthenic syndrome is relatively frequent, occurring in about 1% of patients with small cell lung cancer. PNS can affect any part of the central and peripheral nervous system, the neuromuscular junction, and muscle. They can be isolated or occur in association. In most patients, the neurological disorder develops before the cancer becomes clinically overt and the patient is referred to the neurologist who has the charge of identifying a neurological disorder as paraneoplastic. PNS are usually severely disabling. The most common PNS are Lambert-Eaton myasthenic syndrome (LEMS), subacute cerebellar ataxia, limbic encephalitis (LE), opsoclonus-myoclonus (OM), retinopathies (cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR), Stiff-Person syndrome (SPS), chronic gastrointestinal pseudoobstruction (CGP), sensory neuronopathy (SSN), encephalomyelitis (EM) and dermatomyositis. PNS are caused by autoimmune processes triggered by the cancer and directed against antigens common to both the cancer and the nervous system, designated as onconeural antigens. Due to their high specificity (> 90%), the best way to diagnose a neurological disorder as paraneoplastic is to identify one of the well-characterized anti-onconeural protein antibodies in the patient's serum. In addition, as these antibodies are associated with a restricted range of cancers, they can guide the search for the underlying tumor at a stage when it is frequently not clinically overt. This is a critical point as, to date, the best way to stabilize PNS is to treat the cancer as soon as possible. Unfortunately, about one-third of patients do not have detectable antibodies and 5% to 10% have an atypical antibody that is not well-characterized. As PNS are believed to be immune-mediated, suppression of the immune response represents another treatment approach.
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PMID:Paraneoplastic neurological syndromes. 1748 Feb 25

There are a number of illnesses that can mimic multiple sclerosis (MS). This pretty much includes any pathological process that can reflect injury to the central nervous system either in a transient or progressive basis. Typically, MS presents itself in individuals in their teens up to their late 30s. On occasion, however, one can see MS present in patients in their 60s. However, in retrospect, many of these patients might have had subtle manifestations of MS in their younger years. Visual obscuration or visual loss can be a manifestation of retinal ischemia, retinal migraine, or optic neuritis which might or might not evolve into a clinical picture compatible with MS. Cranial neuropathy, long tract signs, sensory disturbance, and/or gait ataxia can be related to a number of different processes such as illicit drug use, neurosarcoidosis, neuro-Behcet's disease, neuroborreliosis, HIV-related disease, neurosyphilis, vascular occlusive disease including vasculitis, connective tissue disorders, acute disseminated encephalomyelitis (ADEM), idiopathic transverse myelitis, neuromyelitis optica (NMO), or tropical spastic paraparesis. In addition, a constellation of symptoms, with questionable objective findings, along with normal MRI imaging, normal CSF results, and normal evoked response testing, when indicated, might identify a conversion disorder or possibly malingering. There are now established criteria for the diagnosis of MS, but initial presentations can be less than "textbook" in nature. With the advent of immunomodulating therapy, it has become more important to diagnose MS more effectively earlier on in the course of the illness. Prior to specific therapy for MS, astute clinicians did not necessarily move with alacrity to establish the diagnosis in patients with subtle or transient manifestations. This was in recognition of the fact that little could be offered to alter the course of the illness and a number of patients might never experience further problems if they were lucky enough to have their illness go into permanent remission after one minor exacerbation.
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PMID:Differential diagnosis of multiple sclerosis. 1753 52

Lesions in the splenium of the corpus callosum are a rare complication of a variety of clinical conditions including ischemia, trauma, acute disseminated encephalomyelitis, infection, electrolyte imbalances, seizures, and antiepileptic drugs. This report describes a child presenting with hemifield visual color anomia, headache, and papilledema, who was found to have a midline splenial lesion on diffusion-weighted magnetic resonance imaging (MRI). Lumbar puncture revealed elevated intracranial pressure. His symptoms and MRI findings resolved quickly following treatment of his increased intracranial pressure. This is the first report describing an association between intracranial hypertension and a lesion in the splenium of the corpus callosum.
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PMID:Splenial corpus callosum lesion and hemifield visual color anomia associated with intracranial hypertension. 1789 Apr 15

Different pathologic patterns in multiple sclerosis (MS) are reflected by alterations of metabolites in (1)H MR spectroscopy of the brain. Elevated choline (Cho), lactate (Lac), lipids and macromolecules are reliable markers for acute demyelination regardless of the clinical entity (also in acute disseminated encephalomyelitis). N-acetyl-aspartate (NAA) is a suitable marker for neuronal integrity. It is reduced in acute MS lesions and in normal appearing white matter, even distant to acute and chronic-lesions. Recovery from reduced NAA levels to subnormal values during remyelination, and varying time courses of NAA in normal appearing white matter during relapsing remitting disease indicate the value of this spectroscopic marker for monitoring activity and recovery. Inositol (Ins) is increased in chronic MS lesions being a marker for astrocytic gliosis. In viral disease, Cho and Ins are always increased, whereas a reduction of NAA mostly reflects an advanced or a detoriated clinical state. In bacterial brain abscesses, numerous amino acids, lipids and Lac can be elevated. In ischemia, especially the Lac/NAA in comparison with perfusion and diffusion weighted imaging seems to be a new measure for areas of metabolic need, and may help to better characterise the penumbra of the stroke and the final infarct size.
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PMID:(1)H MR spectroscopy of inflammation, infection and ischemia of the brain. 1840 47

The optic nerve is often affected in patients with glaucoma and multiple sclerosis. Conventional MRI can detect nerve damage, but it does not accurately assess the underlying pathologies. Mean diffusivity and diffusion anisotropy indices derived from diffusion tensor imaging have been shown to be sensitive to a variety of central nervous system white matter pathologies. Despite being sensitive, the lack of specificity limits the ability of these measures to differentiate the underlying pathology. Directional (axial and radial) diffusivities, measuring water diffusion parallel and perpendicular to the axonal tracts, have been shown to be specific to axonal and myelin damage in mouse models of optic nerve injury, including retinal ischemia and experimental autoimmune encephalomyelitis. The progression of Wallerian degeneration has also been detected using directional diffusivities after retinal ischemia. However, translating these findings to human optic nerve is technically challenging. The current status of diffusion MRI of human optic nerve, including imaging sequences and protocols, is summarized herein. Despite the lack of a consensus among different groups on the optimal sequence or protocol, increased mean diffusivity and decreased diffusion anisotropy have been observed in injured optic nerve from patients with chronic optic neuritis. From different mouse models of optic nerve injuries to the emerging studies on patients with optic neuritis, directional diffusivities show great potential to be specific biomarkers for axonal and myelin injury.
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PMID:Assessing optic nerve pathology with diffusion MRI: from mouse to human. 1875 87

CD8+ macrophages appear in the central nervous system (CNS) under various pathological conditions such as trauma and ischemia. Furthermore, macrophages expressing CD8 were found in CNS lesions of chronic, but not acute, experimental autoimmune encephalomyelitis (EAE). To further characterize cells with this phenotype, we examined CD8+ macrophages/monocytes in the CNS and peripheral organs during the course of acute and chronic EAE that had been induced by immunization of rats with myelin basic protein and myelin oligodendrocyte glycoprotein, respectively. Counting CD8+ macrophages in CNS lesions revealed that their numbers increased reaching about 60% of total infiltrating macrophages in chronic EAE, while CD8+ macrophages remained less than 5% throughout the course of acute EAE. Unexpectedly, however, higher abundance of CD8+ monocytes/macrophages in the peripheral blood was found in both acute and chronic EAE. Real-time polymerase chain reaction analysis revealed no significant difference in the levels of chemokines and chemokine receptors of blood CD8+ monocytes between acute and chronic EAE. mRNA expression of perforin, a cytotoxic substance, was up-regulated in CD8+ monocytes compared with that of CD8- monocytes in both acute and chronic EAE. These findings suggest that activated CD8+ macrophages may play a cytotoxic role in chronic EAE lesions and that cells other than CD8+ monocytes/macrophages determined the difference in CNS pathology between acute and chronic EAE. Analysis of CD8+ monocytes/macrophages may provide useful information to permit further dissect the pathomechanisms of multiple sclerosis and to develop effective immunotherapies against autoimmune diseases in the CNS.
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PMID:Characterization of CD8-positive macrophages infiltrating the central nervous system of rats with chronic autoimmune encephalomyelitis. 1895 31

Recognition of the importance of the endocannabinoid system in both homeostasis and pathologic responses raised interest recently in the development of therapeutic agents based on this system. The CB(2) receptor, a component of the endocannabinoid system, has significant influence on immune function and inflammatory responses. Inflammatory responses are major contributors to central nervous system (CNS) injury in a variety of diseases. In this report, we present evidence that activation of CB(2) receptors, by selective CB(2) agonists, reduces inflammatory responses that contribute to CNS injury. The studies demonstrate neuroprotective effects in experimental autoimmune encephalomyelitis, a model of multiple sclerosis, and in a murine model of cerebral ischemia/reperfusion injury. In both cases, CB(2) receptor activation results in reduced white cell rolling and adhesion to cerebral microvessels, a reduction in immune cell invasion, and improved neurologic function after insult. In addition, administration of the CB(1) antagonist SR141716A reduces infarct size following ischemia/reperfusion injury. Administration of both a selective CB(2) agonist and a CB(1) antagonist has the unique property of increasing blood flow to the brain during the occlusion period, suggesting an effect on collateral blood flow. In summary, selective CB(2) receptor agonists and CB(1) receptor antagonists have significant potential for neuroprotection in animal models of two devastating diseases that currently lack effective treatment options.
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PMID:Modulation of cannabinoid receptor activation as a neuroprotective strategy for EAE and stroke. 1925 56

Baculovirus immediate early P35 protein is well known for its anti-apoptotic as well as anti-oxidant properties. Mechanism of action of P35 involves inhibition of a vast range of initiator to executioner class of caspases. In addition, P35's role in inhibiting oxidant-induced mitochondrial damage, primarily in the apoptotic pathway, has also been extensively investigated. Elucidation of P35's functions during regulation of programmed cell death (PCD) has led to a renewed focus on exploiting this basic knowledge for clinical and other related applications. This review outlines specific biochemical and genetic pathways where P35 intervenes and regulates rate-limiting steps in the apoptotic signaling cascade. Research efforts are underway to utilize P35 as an agent in regulating apoptosis and under certain circumstances, also explore the therapeutic potential of its anti-oxidant features. One of the major outcomes of recent studies include significantly improved effectiveness of cytochrome P450 directed enzyme pro-drug delivery tools when used in conjunction with P35, which may help in alleviating drug resistance in tumor cells and simultaneously prolonging the cytotoxic effects of anti-cancer drugs. Moreover, applied research carried out recently in the fields of diabetes, ischemia-induced neuronal cell death, experimental autoimmune encephalomyelitis (EAE), multiple sclerosis (MS), inflammatory arthritis, cardiovascular and ocular disorders illustrate P35's utilization across diverse therapeutic areas and will certainly make it an attractive biomolecule for the discovery research.
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PMID:Baculovirus P35 protein: an overview of its applications across multiple therapeutic and biotechnological arenas. 1983 Aug 25

The transcription factor NF-kappaB has diverse functions in the nervous system, depending on the cellular context. NF-kappaB is constitutively activated in glutamatergic neurons. Knockout of p65 or inhibition of neuronal NF-kappaB by super-repressor IkappaB resulted in the loss of neuroprotection and defects in learning and memory. Similarly, p50-/- mice have a lower learning ability and are sensitive to neurotoxins. Activated NF-kappaB can be transported retrogradely from activated synapses to the nucleus to translate short-term processes to long-term changes such as axon growth, which is important for long-term memory. In glia, NF-kappaB is inducible and regulates inflammatory processes that exacerbate diseases such as autoimmune encephalomyelitis, ischemia, and Alzheimer's disease. In summary, inhibition of NF-kappaB in glia might ameliorate disease, whereas activation in neurons might enhance memory. This review focuses on results produced by the analysis of genetic models.
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PMID:NF-kappaB in the nervous system. 2006 5

In the normal brain, cellular types that compose the neurovascular unit, including neurons, astrocytes and endothelial cells express pannexins and connexins, which are protein subunits of two families that form plasma membrane channels. Most available evidence in mammals indicated that endogenously expressed pannexins only form hemichannels, and connexins form both gap junction channels and hemichannels. While gap junction channels connect the cytoplasm of contacting cells and coordinate electrical and metabolic activities, hemichannels communicate intra- and extracellular compartments and serve as diffusional pathways for ions and small molecules. Here, evidence supporting the functional role of hemichannels in the neurovascular unit and white matter under physiological and pathological conditions are reviewed. A sub-threshold acute pathological threatening condition (e.g., stroke and brain infection) leads to glial cell activation, which maintains an active defense and restores the normal function of the neurovascular unit. However, if the stimulus is deleterious, microglia and the endothelium become overactivated, both releasing bioactive molecules (e.g., glutamate, cytokines, prostaglandins and ATP) that increase the activity of astroglial hemichannels, reducing the astrocyte neuroprotective functions, and further reducing neuronal cell viability. Moreover, ATP is known to contribute to myelin degeneration of axons. Consequently, hemichannels might play a relevant role in the excitotoxic response of oligodendrocytes observed in ischemia and encephalomyelitis. Regulated changes in hemichannel permeability in healthy brain cells can have positive consequences in terms of paracrine/autocrine signaling, whereas persistent changes in cells affected by neurological disorders can be detrimental. Therefore, blocking hemichannels expressed by glial cells and/or neurons of the inflamed central nervous system might prevent neurovascular unit dysfunction and neurodegeneration.
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PMID:Hemichannels in the neurovascular unit and white matter under normal and inflamed conditions. 2128 90


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