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

A simple method is described for isolating avian encephalomyelitis virus (AEV) from a bulk amount of proteins and lipids in a homogenate of infected whole chicken embryos. More than 90% of the virus in the homogenate was precipitated by 4% polyethylene glycol (PEG), and the precipitate was free of approximately 90% of the total nonviral protein. When the homogenate was extracted with fluorocarbon, the aqueous fraction retained the full virus infectivity and about 70% of the protein but was free from most lipid materials. A two-step procedure (precipitation of the homogenate by 4% PEG, followed by extraction of the precipitate by fluorocarbon) gave a 50-fold purification of AEV over the original homogenate. The procedure is simple, rapid, and effective in removing nonviral proteins and lipids from host tissues. It is useful as an initial treatment of embryonic materials for the purification of AEV.
 ...
PMID:Use of polyethylene glycol and fluorocarbon for the purification of avian encephalomyelitis virus. 19 74

A rapid and convenient method is described for purifying avian encephalomyelitis virus. Infected embryo homogenate was treated with polyethylene glycol followed by extraction with fluorocarbon. Extracted sample was pelleted at 73,400 x g, resuspended, and subjected to isodensity centrifugation in preformed nonlinear gradient. A distinctive virus band was observed after centrifugation for 120 min at 192,000 x g. The fraction containing the virus band demonstrated the major portion of infectivity and the presence of the virus particles by electron microscopy. The method was reproducible within a limited number of trials.
 ...
PMID:Purification of avian encephalomyelitis virus by ultracentrifugation in a nonlinear cesium chloride gradient. 21 5

A rapid procedure for the purification of egg-grown or field preparations of avian encephalomyelitis virus (AEV) of neural origin is described. Extracts of infected tissues were clarified and then partly purified with trichlorotrifluorethane (Freon TF), and the virus present was concentrated with polyethylene glycol. The concentrates were then re-extracted with Freon, and a portion was labeled with 125iodine. During subsequent purification steps, virus could be readily detected by monitoring for radioactivity, thus eliminating the need to determine the infectivity in individual fractions or to examine for the presence of virions by electron microscopy. Final purification was achieved by cesium-chloride equilibrium or sucrose-velocity-gradient centrifugation. Virus purified in this manner was shown to be free of tissue debris, to be specific for AEV by immune electron microscopy, and to possess structural proteins characteristic of picornaviruses.
 ...
PMID:A rapid procedure for the purification of avian encephalomyelitis viruses. 299 33

Increasing evidence indicates that the cytokines, tumor necrosis factor (TNF), interleukin-1, and/or interferon-gamma, may play a crucial role in the pathogenesis of multiple sclerosis. Several reports demonstrated that inhibition of TNF is highly protective in experimental allergic encephalomyelitis (EAE) when sensitization is accomplished by the passive transfer of myelin basic protein (MBP) sensitized lymphocytes. However, successful protection has not been reported in EAE that is induced by active immunization with MBP. We examined the effects of a TNF inhibitor, dimeric polyethylene glycol linked form of the type I soluble receptor of TNF, PEG-(rsTNF-RI)2, on actively acquired EAE. Treatment with PEG-(rsTNF-RI)2 at 0.3-3 mg/kg every other day or every third day starting on Day 9 postimmunization with MBP during the effector phase of EAE significantly inhibited clinical signs in a dose-dependent manner. Histological examination of the central nervous system indicated that the administration of PEG-(rsTNF-RI)2 reduced, in part, the cellular infiltrate, particularly in the lumbar and sacral regions of the spinal cord. These studies suggest that TNF is a pivotal mediator of the inflammation resulting from the complete immune response induced by active immunization with MBP.
 ...
PMID:Inhibition of tumor necrosis factor is protective against neurologic dysfunction after active immunization of Lewis rats with myelin basic protein. 753 20

1. Circulating corticosterone, interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF alpha) activities in serum of Lewis and Wistar rats were measured following injection of lipopolysaccharide (LPS). IL-1 was measured as 'lymphocyte activation factor' (LAF) activity following precipitation of inhibitory activity with polyethylene glycol. TNF alpha activity was measured as cytotoxic activity. 2. Compared to the Wistar, the Lewis rat had higher circulating LAF and TNF activities following LPS, and release of both cytokines was prolonged in this strain. 3. Corticosterone increases in response to LPS were less in the Lewis than in the Wistar rat following the initial peak at 1 h; basal corticosterone was lower in the Lewis rat. 4. Adrenalectomized Lewis rats had even greater amounts of circulating LAF and TNF activities following LPS than did intact animals; the effect of adrenalectomy was not however mimicked by acute treatment with the steroid receptor antagonist, RU486, suggesting that endogenous corticosteroids did not acutely control cytokine release. 5. Although in vivo administration of anti-murine IL-1 alpha antiserum significantly lowered LAF activity of serum, circulating corticosterone in response to LPS was not affected. Similarly, treatment with anti-murine TNF alpha monoclonal antibody (mAb) abrogated TNF activity without affecting corticosterone, suggesting that other mediators may be responsible for corticosterone release following LPS. 6. This 'overproduction' of inflammatory cytokines together with lower circulating corticosterone may contribute to the susceptibility of the Lewis rat to diseases such as adjuvant arthritis or experimental allergic encephalomyelitis.
 ...
PMID:Serum corticosterone, interleukin-1 and tumour necrosis factor in rat experimental endotoxaemia: comparison between Lewis and Wistar strains. 824 62

The effect of a novel TNF binding protein (TNFbp), a polyethylene glycol-linked form of the type I soluble receptor of TNF, on the expression of adhesion molecules has been investigated with a passive transfer model of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. The expression of L-selectin, VLA-4 and LFA-1 on spleen cells of EAE animals treated with TNFbp or saline was examined by FACS analysis. The expression of VCAM-1 and ICAM-1 was investigated by immunochemistry in spinal cord tissue of SJL/J mice with EAE. In animals sensitized for EAE and treated with TNFbp, the expression of VCAM-1 in the central nervous system as well as VLA-4 on spleen cells was clearly diminished. Reduction in VCAM-1 staining and VLA-4 expression corresponded to inhibition of inflammation in the spinal cord and to prevention of clinical signs of EAE. The results have also shown that myelin basic protein responses as well as non-antigen-specific responses were not diminished in animals treated with TNFbp. The findings suggest that TNFbp might prevent EAE development by modulating the expression of VCAM-1 and VLA-4.
 ...
PMID:Suppression of experimental autoimmune encephalomyelitis with a TNF binding protein (TNFbp) correlates with down-regulation of VCAM-1/VLA-4. 964 85

High-dose glucocorticosteroid hormones are a mainstay in the treatment of relapses in multiple sclerosis. We searched for a way to deliver ultra high doses of glucocorticosteroids to the CNS of rats with experimental autoimmune encephalomyelitis (EAE) using a novel formulation of polyethylene glycol (PEG)-coated long-circulating liposomes encapsulating prednisolone (predni solone liposomes, PL). 3H-labelled PL showed selective targeting to the inflamed CNS, where up to 4.5-fold higher radioactivity was achieved than in healthy control animals. HPLC revealed much higher and more persistent levels of prednisolone in spinal cord after PL compared with an equal dose of free prednisolone. Gold-labelled liposomes could be detected in the target tissue, mostly taken up by macrophages (Mphi), microglial cells and astrocytes. Blood-brain barrier disruption was greatly reduced by 10 mg/kg PL, which was superior to a 5-fold higher dose of free methylprednisolone (MP). PL was also superior to MP in diminishing T-cell infiltration by induction of T-cell apoptosis in spinal cord. Mphi infiltration was clearly decreased only by PL. The percentage of tumour necrosis factor-alpha (TNF-alpha)-positive T cells or Mphi was greatly reduced by PL and by MP. No adverse effects on glial cells were detected. A single injection of PL clearly ameliorated the course of adoptive transfer EAE and EAE induced by immunization. In conclusion, PL is a highly effective drug in treatment of EAE, and is superior to a 5-fold higher dose of free MP, possibly by means of drug targeting. These findings may have implications for future therapy of autoimmune disorders such as multiple sclerosis.
 ...
PMID:Drug targeting by long-circulating liposomal glucocorticosteroids increases therapeutic efficacy in a model of multiple sclerosis. 1280 1

Multiple sclerosis (MS) relapses are treated with high-dose IV glucocorticosteroids. Here we investigated mechanisms of long-circulating polyethylene glycol-coated liposomes encapsulating prednisolone (PL) in adoptive transfer experimental autoimmune encephalomyelitis. Rats received IV 10 mg/kg PL 6, 18, or 42 hr before sacrifice at disease maximum. In formalin-fixed, paraffin-embedded spinal cord we employed a nonfluorescent immunohistochemical (IHC) double labeling. We stained for tumor necrosis factor-alpha (TNF-alpha) in combination with a T-cell antigen. Compared with PBS-containing liposomes, PL at 18 hr, and more at 42 hr, significantly reduced the rate of TNF-alpha double-labeled T-cells. This correlated with an ameliorated disease score at day 5 after PL 42 hr. Our results help to further understand mechanisms of action of drug targeting by liposomal steroids, with possible implications for treatment of autoimmune disorders such as MS.
 ...
PMID:Intravenous liposomal prednisolone downregulates in situ TNF-alpha production by T-cells in experimental autoimmune encephalomyelitis. 1292 50

Integrin alpha4beta1 plays an important role in inflammatory processes by regulating the migration of leukocytes into inflamed tissues. Previously, we identified BIO5192 [2(S)-{[1-(3,5-dichloro-benzenesulfonyl)-pyrrolidine-2(S)-carbonyl]-amino}-4-[4-methyl-2(S)-(methyl-{2-[4-(3-o-tolyl-ureido)-phenyl]-acetyl}-amino)-pentanoylamino]-butyric acid], a highly selective and potent (K(D) of 9 pM) small molecule inhibitor of alpha4beta1. Although BIO5192 is efficacious in various animal models of inflammatory disease, high doses and daily treatment of the compound are needed to achieve a therapeutic effect because of its relatively short serum half-life. To address this issue, polyethylene glycol modification (PEGylation) was used as an approach to improve systemic exposure. BIO5192 was PEGylated by a targeted approach in which derivatizable amino groups were incorporated into the molecule. Two sites were identified that could be modified, and from these, five PEGylated compounds were synthesized and characterized. One compound, 2a-PEG (K(D) of 19 pM), was selected for in vivo studies. The pharmacokinetic and pharmacodynamic properties of 2a-PEG were dramatically improved relative to the unmodified compound. The PEGylated compound was efficacious in a rat model of experimental autoimmune encephalomyelitis at a 30-fold lower molar dose than the parent compound and required only a once-a-week dosing regimen compared with a daily treatment for BIO5192. Compound 2a-PEG was highly selective for alpha4beta1. These studies demonstrate the feasibility of PEGylation of alpha4beta1-targeted small molecules with retention of activity in vitro and in vivo. 2a-PEG, and related compounds, will be valuable reagents for assessing alpha4beta1 biology and may provide a new therapeutic approach to treatment of human inflammatory diseases.
 ...
PMID:Design, synthesis, and analysis of a polyethelene glycol-modified (PEGylated) small molecule inhibitor of integrin {alpha}4{beta}1 with improved pharmaceutical properties. 1548 95

An avian encephalomyelitis virus (AEV) antigen, prepared from the gastrointestinal tract of infected chick embryos and partially purified and concentrated by chloroform and polyethylene glycol treatments, exhibited the highest reactivity in the agar-gel precipitin test (AGPT). Antigen used in the passive haemagglutination test (PHAT) that was purified and concentrated yielded higher antibody titres than when untreated crude antigens were used. The use of the AGPT, PHAT and embryo susceptibility test (EST) on chicken breeding flocks with and without a history of previous vaccination against AE revealed that the PHAT was more sensitive in detecting AEV antibodies than the AGPT. The sensitivity of the PHAT was nearly equal to the EST. No correlation was found between the results of the AGPT and the immune status of a flock judged by the EST.
 ...
PMID:Studies on the serological detection of antibodies to avian encephalomyelitis virus. 1877 Jan 90


1 2 Next >>