Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system with many similarities to multiple sclerosis. The main effector cells involved are CD4+ T cells, recognizing encephalitogenic epitopes within the central nervous system, and macrophages, both of which secrete proinflammatory cytokines, such as IFN-gamma and TNF. Studies have shown that immunomodulation of this inflammatory response by anti-inflammatory cytokines (IL-4, IL-10, IFN-beta, and TGF-beta) can reduce clinical severity in EAE. The importance of TNF in EAE has been demonstrated by using soluble TNF-receptor molecules to inhibit EAE. However, the limitation of this type of therapy is the necessity for frequent administration of cytokine proteins due to their short biologic half-life. This study demonstrates that EAE can be inhibited by a single injection of therapeutic cytokine (IL-4, IFN-beta, and TGF-beta) DNA-cationic liposome complex directly into the central nervous system. DNA coding for a novel, dimeric form of human p75 TNF receptor also ameliorated clinical EAE. Local administration of DNA-cationic liposome complex has identified gene targets that may be more efficiently exploited using vectors producing more stable expression for effective treatment of neuroimmunologic disease.
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PMID:Cytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid DNA-cationic liposome complex into the central nervous system. 959 Feb 71

Neuroborreliosis, a manifestation of infection with the spirochete Borellia burgdorferi, has become the most frequently recognised arthropod-borne infection of the nervous system in Europe and the USA. The best criterion of an early infection with B. burgdorferi is erythema migrans (EM), but this is present in only about 40-60% of patients with validated borreliosis. Therefore use of the duration of the disease as a classification criterion for neuroborreliosis is increasing, the chronic form being distinguished from the acute when symptoms persist for more than 6 months. The diverse manifestations of neuroborreliosis require that it be included in the differential diagnosis of many neurological disorders. In Europe, meningopolyradiculoneuritis (Bannwarth's syndrome) represents the most common manifestation of acute neuroborreliosis, with the facial nerve being affected much more frequently than the other cranial nerves. Clinical symptoms affecting the central nervous system are rarely observed and then mostly in chronic courses. By far the most common manifestation of chronic neuroborreliosis is encephalomyelitis with spastic-ataxic disturbances and a disturbance of micturition. The current diagnosis of neuroborreliosis is a clinical one, which has to be confirmed by laboratory testing. In most patients, examination of the cerebrospinal fluid (CSF) reveals lymphocytic pleocytosis, damage to the blood-CSF-barrier and an intrathecal synthesis immunoglobulin (Ig) M, IgG, and sometimes IgA. Confirmation of a borrelial infection of the nervous system requires demonstration of an intrathecal synthesis of borrelial-specific antibodies in the CSF or detection of borrelial DNA in the CSF by polymerase chain reaction (PCR). There is no generally accepted therapeutic regime for the treatment of neuroborreliosis, but recent studies have shown ceftriaxone 2 g/day and cefotaxime 6 g/day to be effective in acute and chronic courses. Penicillin G 20 mega units/day and doxycycline 200 mg/day may be suitable for uncomplicated meningopolyneuritis, without involvement of the central nervous system. The durationof treatment--at least 2 weeks in the acute forms and 3 weeks in the chronic forms of neuroborreliosis--is very important for successful treatment. Corticosteroids are recommended only for patients with severe pain that does not respond to antibiotics an analgesics.
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PMID:Neuroborreliosis. 961 4

Any headache in the course of Lyme disease could be an early manifestation of invasion of the CNS by spirochaetes. The most characteristic symptoms of early neuroborreliosis are meningitis with cranial or peripheral neuropathies connected with radiculopathies, less common are encephalitis and myelitis, neuropathies, polyneuropathies, encephalopathies. Encephalomyelitis is the most serious form of neuroborreliosis. From the pathophysiologic point of view all cranial and peripheral neuropathies are forms of mononeuritis multiplex. Encephalopathy is due to neuroimmunomodulators, like lymphokins and or by toxico-metabolic effect could be connected with each form of systemic borreliosis. Certain diagnosis of neuroborreliosis is based on culturing of B. burgdorferi from CSF, detection of specific antispirochaetal antibodies produced in the subarachnoid space, detection of activated lymphocytes B producing specific antibodies, detection in CSF of other antigens of B. burgdorferi or DNA sequences.
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PMID:[Neurologic borreliosis]. 963 83

Intracellular adhesion molecule-1 (ICAM-1) plays an important role in the cascade of adhesion events in the homing of inflammatory cells to the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE) and in multiple sclerosis (MS). Two single-base ICAM-1 polymorphisms have been described, in exons 4 and 6, changing codons 241 and 469 in the ICAM-1 gene, respectively. Both polymorphisms result in amino acid changes and can potentially lead to different interactions of ICAM-1 with its ligands. To detect ICAM-1 gene polymorphisms in MS, we have developed a highly sensitive and site-specific, two-stage, nested polymerase chain reaction. Genomic DNA was extracted from blood cells of 79 MS patients and 68 control subjects. The results were confirmed by direct dideoxy chain termination sequencing. The frequency of exon 6 allele T was found to be significantly higher in MS patients than in controls (68% vs 49%). Most interesting, the frequency of exon 6 homozygote K469 was significantly higher in MS patients than in controls (53% vs 34%). Higher frequency of the K469 genotype was found to be independent of possible linkage with the previously described MS susceptibility factor, the HLA class II DR2 allele. In the present study, we have shown for the first time the ICAM-1 gene polymorphisms in MS. The results indicate increased frequency of ICAM-1 exon 6 allele T in MS patients, which may contribute to the MS genetics background.
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PMID:Multiple sclerosis: the increased frequency of the ICAM-1 exon 6 gene point mutation genetic type K469. 1066 8

Peroxynitrite and hydroxyl radicals are potent initiators of DNA single strand breakage, which is an obligatory stimulus for the activation of the nuclear enzyme poly(ADP-ribose)synthetase (PARS). Rapid activation of PARS depletes the intracellular concentration of its substrate, NAD+, slowing the rate of glycolysis, electron transport and ATP formation. This process can result in acute cell dysfunction and cell necrosis. Accordingly, inhibitors of PARS protect against cell death under these conditions. In addition to the direct cytotoxic pathway regulated by DNA injury and PARS activation, PARS also appears to modulate the course of inflammation by regulating the expression of a number of genes, including the gene for intercellular adhesion molecule 1, collagenase and the inducible nitric oxide synthase. The research into the role of PARS in inflammatory conditions is now supported by novel tools, such as novel, potent inhibitors of PARS, and genetically engineered animals lacking the gene for PARS. In vivo data demonstrate that inhibition of PARS protects against various forms of inflammation, including zymosan or endotoxin induced multiple organ failure, arthritis, allergic encephalomyelitis, and diabetic islet cell destruction. Pharmacological inhibition of PARS may be a promising novel approach for the experimental therapy of various forms of inflammation.
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PMID:Role of poly(ADP-ribose)synthetase in inflammation. 968 9

Morphological studies have shown that macrophages and microglia undergo apoptosis in the central nervous system (CNS) in acute experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. To assess the relative levels of macrophage and microglial apoptosis, and the molecular mechanisms involved in this process, we used three-colour flow cytometry to identify CD45lowCD11b/c+ microglial cells and CD45highCD11b/c+ macrophages in the inflammatory cells isolated from the spinal cords of Lewis rats 13 days after immunization with myelin basic protein (MBP) and complete Freund's adjuvant. Simultaneously, we analyzed the DNA content of these cell populations to assess the proportions of cells undergoing apoptosis and in different stages of the cell cycle or examined their expression of three apoptosis-regulating proteins, i.e. Fas (CD95), Fas ligand (FasL) and Bcl-2. Microglia were highly vulnerable to apoptosis and were over-represented in the apoptotic population. Macrophages were less susceptible to apoptosis than microglia and underwent mitosis more frequently than microglia. The different susceptibilities of microglia and macrophages to apoptosis did not appear to be due to variations in Fas, FasL or Bcl-2 expression, as the proportions of microglia and macrophages expressing these proteins were similar, and were relatively high. Furthermore, in contrast to T cell apoptosis, apoptosis of microglia/macrophages did not occur more frequently in cells expressing Fas or FasL, or less frequently in cells expressing Bcl-2. These results indicate that the apoptosis of microglia and CNS macrophages in EAE is not mediated through the Fas pathway, and that Bcl-2 expression does not protect them from apoptosis. Expression of FasL by macrophages and microglia may contribute to the pathogenesis and immunoregulation of EAE through interactions with Fas+ oligodendrocytes and Fas+ T cells. The high level of microglial apoptosis in EAE indicates that microglial apoptosis may be an important homeostatic mechanism for controlling the number of microglia in the CNS following microglial activation and proliferation.
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PMID:Microglia are more susceptible than macrophages to apoptosis in the central nervous system in experimental autoimmune encephalomyelitis through a mechanism not involving Fas (CD95). 970 Oct 31

Relapsing-remitting experimental allergic encephalomyelitis (R-EAE) is an animal model for multiple sclerosis (MS). Many potential immunomodulatory strategies for MS have been used first in EAE to assess their effectiveness. Recently, the injection of plasmid DNA has been shown to induce potent humoral and cellular immune responses. The primary aim of our experiments reported here was to determine if vaccination with cDNAs encoding myelin proteolipid protein (PLP) could prime for a PLP-specific immune response and affect subsequent R-EAE. We constructed cDNAs encoding whole PLP (pPLP(all)) or encephalitogenic epitopes PLP(139-151) (pPLP(139-151)) and PLP(178-191) (pPLP(178-191)). Following DNA injection, we induced R-EAE in SJL/J mice using PLP(139-151) or PLP(178-191) peptides in adjuvant. All 3 plasmid constructs enhanced R-EAE induced with PLP(139-151), and injection of mice with pPLP(all) increased R-EAE induced with PLP(178-191). DNA immunization induced higher PLP peptide-specific lymphoproliferative responses than did vector alone following R-EAE induction with IgG1 or IgG2b antibody responses. These data suggest that DNA immunization of PLP can modulate immune responses, leading to enhancement of R-EAE.
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PMID:Enhancement of experimental allergic encephalomyelitis (EAE) by DNA immunization with myelin proteolipid protein (PLP) plasmid DNA. 972 Apr 91

Demonstration of the direct involvement of cranial blood vessels by varicella zoster virus (VZV) is facilitated by immunohistochemistry (IHC), in situ hybridization (ISH) and polymerase chain reaction (PCR) techniques. The extent to which an inflammatory vasculitis serves as the pathogenic mechanism for VZV encephalomyelitis (VZVE) is still, however, debated. Most VZVE patients are immunocompromised and show little inflammation, either pre-mortem in cerebrospinal fluid (CSF) or at autopsy. We describe an HIV-positive patient with a moderately depressed CD4 count (304) who presented with massively elevated CSF protein (1800 mg/dl), bloody CSF and pleocytosis (1300 white blood cells (WBC)/mm3). His CSF was positive for VZV DNA by PCR. He was treated with acyclovir and foscarnet, but died. At autopsy, an unusually widespread, inflammatory, transmural vasculitis caused by VZV affected meningeal vessels at virtually all brain stem and spinal cord levels, causing multiple subpial hemorrhages and necrosis. Virus DNA in multiple areas of brain, brainstem and spinal cord was readily revealed by PCR, but not by the presence of viral inclusions, IHC or ISH. This case, with a clinically confusing presentation for VZVE, illustrates the extensive, albeit infrequent, degree of necrotizing vasculitis and CSF abnormalities that VZV is capable of producing. Antiviral therapy may have inhibited VZV genome replication and subsequent antigen production, resulting in negative ISH and IHC studies, but generated increased VZV genomic fragments that were detectable by the more sensitive PCR technique.
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PMID:Profound cerebrospinal fluid pleocytosis and Froin's Syndrome secondary to widespread necrotizing vasculitis in an HIV-positive patient with varicella zoster virus encephalomyelitis. 974 10

DNA vaccination represents a novel means of expressing Ag in vivo for the generation of both humoral and cellular immune responses. The current study uses this technology to elicit protective immunity against experimental autoimmune encephalomyelitis (EAE), a T cell-mediated autoimmune disease of the central nervous system that serves as an experimental model for multiple sclerosis. RT-PCR verified by Southern blotting and sequencing of PCR products of four different C-C chemokines, macrophage-inflammatory protein-1alpha (MIP-1alpha), monocyte-chemotactic protein-1 (MCP-1), MIP-1beta, and RANTES, were performed on brain samples from EAE rats to evaluate mRNA transcription at different stages of disease. Each PCR product was then used as a construct for naked DNA vaccination. The subsequent in vivo immune response to MIP-1alpha or MCP-1 DNA vaccines prevented EAE, even if disease was induced 2 mo after administration of naked DNA vaccines. In contrast, administration of the MIP-1beta naked DNA significantly aggravated the disease. Generation of in vivo immune response to RANTES naked DNA had no notable effect on EAE. MIP-1alpha, MCP-1, and MIP-1beta mRNA transcription in EAE brains peaked at the onset of disease and declined during its remission, whereas RANTES transcription increased in EAE brains only following recovery. Immunization of CFA without the encephalitogenic epitope did not elicit the anti-C-C chemokine regulatory response in DNA-vaccinated rats. Thus, modulation of EAE with C-C chemokine DNA vaccines is dependent on targeting chemokines that are highly transcribed at the site of inflammation at the onset of disease.
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PMID:Long-lasting protective immunity to experimental autoimmune encephalomyelitis following vaccination with naked DNA encoding C-C chemokines. 978 Jan 52

The primary lesions of eastern equine encephalomyelitis (EEE) virus infection in the horse are limited to the brain and spinal cord. Intestinal lesions in addition to the changes in the central nervous system were found in a 6-month-old male Tennessee Walking Horse. One week prior to death, this colt was vaccinated for EEE virus, western equine encephalomyelitis virus, influenza virus, equine rhinopneumonitis virus, and tetanus. The clinical signs consisted of ataxia and rear-end weakness, with a body temperature of 102.8 F. Gross lesions consisted of yellowish discoloration, swelling, edema, and hemorrhage of the brain stem and dark discoloration of the gray matter of the spinal cord. Microscopic lesions in the small intestine were mainly in the muscular layer and consisted of multifocal areas of myonecrosis and lymphomonocytic infiltration with a few focal areas of mild fibrous connective tissue proliferation. Occasional focal mild perivascular lymphocytic infiltration was observed in the submucosa. Lesions in the brain and spinal cord consisted of widespread areas of perivascular lymphomonocytic cuffing, focal areas of necrosis, neutrophilic infiltration, hemorrhage, neuronal degeneration, and gliosis. Hepatic changes consisted of periportal lymphocytic infiltration and mild vacuolar degeneration of hepatocytes. EEE virus was isolated from the intestine and detected by DNA in situ hybridization.
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PMID:Intestinal lesions in a horse associated with eastern equine encephalomyelitis virus infection. 982 95


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