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)

Magnetic resonance imaging (MRI) of the brain was studied in 35 patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), 19 HTLV-I seropositive carriers without HAM/TSP (non-HAM/TSP carriers), 18 patients with HTLV-I seronegative spastic spinal paraparesis (SSP), and 82 HTLV-I seronegative controls with other neurological disorders. The incidence of white matter lesions was significantly higher in HAM/TSP (66%) than in the controls (23%) and SSP (11%). HAM/TSP exceeded non-HAM/TSP carriers significantly in the incidence of multiple white matter lesions (37% vs 10%). HAM/TSP affected the deep and subcortical cerebral white matter multifocally, sparing the periventricular regions. None of the lesions were enhanced by gadolinium-DTPA. HAM/TSP patients with the white matter lesions had both a longer duration of disease and a greater disability than did those without lesions. The white matter lesions gradually increased in number, as the disability status became worse, in spite of the high dose corticosteroid treatment. All these observations suggest that the MRI abnormalities of the HAM/TSP brain may reflect the chronic perivascular inflammation with progressive gliosis (chronic disseminated encephalomyelitis). We propose that brain MRI can be successfully utilized as a reliable and non-invasive measure for following the disease progression in HAM/TSP.
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PMID:Leukoencephalopathy in HTLV-I-associated myelopathy/tropical spastic paraparesis: MRI analysis and a two year follow-up study after corticosteroid therapy. 177 38

Uncertainty regarding pathogenic mechanisms has been a major impediment to effective prevention and treatment for human neurologic diseases such as multiple sclerosis, tropical spastic paraparesis, and AIDS demyelinating disease. Here, we implicate lymphotoxin (LT) (tumor necrosis factor beta [TNF-beta]) and TNF-alpha in experimental allergic encephalomyelitis (EAE), a murine model of an autoimmune demyelinating disease. In this communication, we report that treatment of recipient mice with an antibody that neutralizes LT and TNF-alpha prevents transfer of clone-mediated EAE. LNC-8, a myelin basic protein-specific T cell line, produces high levels of LT and TNF-alpha after activation by concanavalin A, antibody to the CD-3 epsilon component of the T cell receptor, or myelin basic protein presented in the context of syngeneic spleen cells. LNC-8 cells transfer clinical signs of EAE. When LNC-8 recipient mice were also treated with TN3.19.12, a monoclonal antibody that neutralizes LT and TNF-alpha, the severity of the transferred EAE was reduced, while control antibodies did not alter the disease. The effect of anti-LT/TNF-alpha treatment was long lived and has been sustained for 5 mo. These findings suggest that LT and TNF-alpha and the T cells that produce them play an important role in EAE.
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PMID:An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. 221 48

Human T-lymphotropic virus type I (HTLV-I), the etiological agent of adult T-cell leukemia/lymphoma, also appears to be the cause of tropical spastic paraparesis, a chronic myelopathy reported in several different regions of the world. The prevalence of antibodies to HTLV-I in patients with chronic neurodegenerative disorders other than tropical spastic paraparesis and in patients with some muscle inflammatory disorders has been investigated. IgG antibodies to HTLV-I were measured in the sera and/or cerebrospinal fluid from 82 Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia, 164 Guamanian normal controls, 10 patients with kuru from the Eastern Highlands of Papua New Guinea, 4 patients with Viliuisk encephalomyelitis from the Iakut region of eastern Siberia, 45 Italian patients with multiple sclerosis, and 56 patients with polymyositis (49 from the United States and 7 from Jamaica). As determined by enzyme-linked immunosorbent assay, Western immunoblot, and gelatin particle agglutination techniques, serological evidence of HTLV-I infection was found in 1 patient with amyotrophic lateral sclerosis and 1 control subject from Guam, and in 1 patient from the United States and all 7 Jamaican patients with polymyositis. Except for the high seropositivity rate among the group of Jamaican patients with polymyositis, our data indicate that HTLV-I is an unlikely causative agent in the spectrum of the neurological diseases examined. The seropositivity of the 7 Jamaican patients with polymyositis requires further study.
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PMID:Seroprevalence of antibodies to HTLV-I in patients with chronic neurological disorders other than tropical spastic paraparesis. 289 13

The consequences of human retroviral infections have had an unprecedented impact on the medical, scientific, and social institutions of the last two decades of this century. The nervous system as an end target organ figures prominently in the constellation of diseases associated with HTLV and HIV infection and numerous syndrome complexes have been recognized that reflect dysfunction of the brain, spinal cord, nerve roots, peripheral nerves, or muscle. HAM/TSP, associated with HTLV-I and rarely with HTLV-II infections, and encephalomyelitis, associated with HIV infection, may present with clinical, laboratory, neuroelectrophysiologic, and neuroimaging features closely resembling MS. A careful systematic search for associated disease processes and review of the medical history, however should raise the suspicion of possible retroviral infection. In the appropriate setting, because of the pleiotropy in disease expression and the high prevalence of retroviral infection in many areas of the United States, clinicians should have a low threshold for ordering diagnostic testing for HIV and HTLV when considering a retroviral cause for a neurologic disorder. The retroviruses are pervasive throughout the vertebrate subphylum and share common elements within their genome that encode for promoters and structural proteins and are distinguished from each other by sets of transactivating and regulating genes. The latter group of genes serve to regulate viral replication by the induction and post-transcriptional and post-translational modification of retrovirally encoded gene products. In addition, the transactivating gene products can activate and upregulate the expression of a variety of host cellular genes, many of which possess immune-related functions. The viral particle or specific components of certain viral structural proteins may be directly toxic to neural tissues. Also, during the replicative phase, retroviruses are recognized by host defense mechanisms, which mount considerable cellular and humoral immune responses. The spectrum of retroviral-associated neurologic diseases therefore may represent a complex interaction among viral antigen-induced immunity, the production of neurotoxic viral peptides, and the abnormal induction and expression of cellular genes with potent bioactivity.
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PMID:Human retroviruses and demyelinating diseases. 773 6

Identification of the localization of human T lymphotrophic virus type I (HTLV-I) proviral DNA in the central nervous system (CNS) is crucial to the understanding of the pathogenesis of HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) pathogenesis. We have developed a sensitive detection method, called two-step polymerase chain reaction (PCR) in situ hybridization, which enabled us to detect the HTLV-I proviral DNA in paraffin-embedded spinal cord tissue sections from HAM/TSP patients. HTLV-I proviral DNA was detected only in the nucleus of lymphocytes that had infiltrated into the spinal cord. However, no proviral DNA was amplified in any neuronal cells, including neurons and glial cells. This indicates that the demyelination of the spinal cord by HTLV-I as a result of viral infection of oligodendrocytes or neuronal cells is unlikely. The T cell receptor V beta gene sequence from lymphocytes in the spinal cord lesions taken from the same HAM/TSP autopsy cases revealed unique and restricted CDR3 motifs, CASSLXG(G) (one-letter amino acid. X is any amino acid), CASSPT(G), and CASSGRL which are similar to those described in T cells from brain lesions of multiple sclerosis (MS) and in a rat T cell clone derived from experimental allergic encephalomyelitis (EAE) lesions. The present results suggest that T cells containing restricted V beta CDR3 motifs, which are also found in MS and EAE, become activated upon HTLV-I infection and infiltrate into the spinal cord lesions of HAM/TSP patients.
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PMID:Detection of human T lymphotrophic virus type I (HTLV-I) proviral DNA and analysis of T cell receptor V beta CDR3 sequences in spinal cord lesions of HTLV-I-associated myelopathy/tropical spastic paraparesis. 806 35

Human T-cell lymphotropic virus type I (HTLV-I) induces a chronic demyelinating disease known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). While only 0.25% of HTLV-I-infected individuals develop HAM/TSP, the mechanisms responsible for the progression of an HTLV-I carrier state to clinical disease are not clear. In particular, no specific sequence differences have been found between HTLV-I recovered from HAM patients and HTLV-I-infected carriers. Since CD4 T cells are the major reservoir of the virus, at least three hypotheses implicating CD4 T cells directly or indirectly have been proposed: 1) The cytotoxic hypothesis predicts that activated and HTLV-I-infected CD4 T cells migrate to the CNS and infect resident cells. Cytotoxic CD8 T cells may then recognize viral antigens on HTLV-I-infected CNS cells causing a cellularly mediated cytotoxic demyelination. 2) The autoimmune hypothesis predicts that either (a) virally reactive T cells crossreact with a CNS antigen, or (b) random infection of CD4 T cells eventually results in the infection of CNS-autoreactive CD4 T cells that, by virtue of the productive HTLV-I infection, become activated, expand and migrate to the CNS, where they encounter their antigen. This results in a specific immune response and demyelination, as is known to occur in experimental autoimmune encephalomyelitis. 3) The bystander damage hypothesis does not implicate a specific response against CNS cells. Instead this hypothesis suggests that the presence of IFN-gamma-secreting HTLV-I-infected CD4 T cells and their recognition by virally specific CD8 T cells in the CNS induce microglia to secrete cytokines, such as TNF-alpha, which may be toxic for the myelin.
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PMID:Pathogenesis of chronic progressive myelopathy associated with human T-cell lymphotropic virus type I. 917 44

Myelin basic protein (MBP) is a major component of the myelin sheath of both the central and peripheral nervous systems. A number of neurological diseases in humans are associated with demyelination of the central and/or peripheral nervous systems, including multiple sclerosis and its variants such as acute disseminated encephalomyelitis (AD), acute hemorrhagic leukoencephalopathy, and idiopathic polyneuritis (Guilliame-Barre syndrome), as well as tropical spastic paraparesis (TSP), and progressive multifocal leukoencephalopathy (PML). Multiple sclerosis (MS) is perhaps the most common demyelinating disease and is one of great importance to the clinical neurologist. The underlying cause of the demyelination seen in multiple sclerosis patients is unknown. However, patients frequently have unusually high antibody titers to a number of common viruses, leading to speculation that viral infections may participate in the pathogenesis of MS. On the other hand, studies on maternal and paternal twins have suggested the involvement of genetic factors in the predisposition of an individual toward developing MS. PML, once a rare demyelinating disease of elderly patients with lymphoproliferative disorders, is now a much more common disease affecting patients of all ages due to the increasingly widespread use of immunosuppressive chemotherapy and the prevalence of AIDS. PML is the result of productive infection of oligodendrocytes, the myelin producing cells of the CNS, with the human polyomavirus, JCV. In this article, we have focused our attention on PML, and the role of JCV in disrupting myelin sheaths by affecting myelin basic gene expression, ultimately leading to demyelination.
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PMID:Human polyomavirus JCV and expression of myelin genes. 1087 94

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