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 a T cell-mediated autoimmune disease. It is widely used as an animal model of multiple sclerosis (MS). We studied the prophylactic effects of FK 506 electrophysiologically and immunohistochemically in acute EAE. Female Lewis rats were sensitized with guinea pig spinal cord in complete Freund's adjuvant. FK 506 suspended in distilled water was orally administered at 1.0, 3.2, 5.0 or 10.0 mg/kg per day for 12 successive days starting from the day of sensitization. A placebo was used as the control. Administration of FK 506 at doses of 3.2 mg/kg per day and over significantly delayed the onset of clinical signs. However, the FK 506 group showed a relapse or a chronic state following the onset of EAE. We made a time course recording of cortical somatosensory evoked potential (cortical SEP: P 15). P 15 latency in the placebo group was significantly delayed in accordance with the clinical signs and showed immediate improvement upon recovery. Prolongation of P 15 latency in the FK 506 group also occurred concomitantly with the clinical signs, but the delay continued after the loss of symptoms as well. After the onset of EAE, the infiltrating lymphocyte subset was examined by the avidin-biotin peroxidase complex (ABC) method in the lumbar spinal cord. In the placebo group, the number of OX3+ (Ia) cells and the W 3 25+: OX8+ (helper/inducer T: suppressor/cytotoxic T) ratio clearly reflected the development and remission of EAE. In the FK 506 group, however, increases in OX8+ lymphocytes were observed irrespective of clinical sign fluctuation, and there were corresponding decreases in the W 3/25+: OX8+ ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of novel immunosuppressant FK 506 in acute experimental allergic encephalomyelitis]. 169 82

FK506, a new immunosuppressive agent, was given intramuscularly to rats for 12 days, starting on the day of type II collagen immunization. FK506 in doses of 0.32 mg/kg or more suppressed arthritis and also suppressed humoral and skin test response to type II collagen. FK506 suppressed arthritis only when given during the afferent limbs of immune response (0-4 days), whereas the drug was only marginally effective when treatment was started during the efferent limbs of immune response (7-11 days). FK506-induced immunosuppression continued and/or was maintained throughout the experiments (50 days). These rats immunized with type II collagen and treated with FK506 failed to develop arthritis even following a secondary immunization 50 days later but were fully capable of developing experimental allergic encephalomyelitis. This result suggest that FK506-treated rats develop specific unresponsiveness toward the type II collagen. It is concluded that FK506 is a strong immunosuppressive drug on collagen-induced arthritis.
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PMID:Immunosuppressive effect of FK506 on collagen-induced arthritis in rats. 244 10

A comparative study was carried out between cyclosporine and a new immunosuppressive agent, FK506, isolated from the Streptomyces organism. This agent has the capacities to suppress the development of S-antigen-induced experimental autoimmune uveoretinitis (EAU) as well as immune responses to S-antigen in rats immunized with the antigen. When administered daily beginning on the day of immunization and for 14 days thereafter, FK506 at doses between 0.1 and 1 mg/kg suppressed EAU in a dose-dependent manner. Complete inhibition of EAU was achieved at doses of 1, 3 and 10 mg/kg. Cyclosporine (1-20 mg/kg) also produced a dose-dependent suppression of EAU and only the highest dose (20 mg/kg) caused complete inhibition of the disease. On the basis of the dose-response study, the capacity of FK506 in preventing EAU induction is 10-30 times more intense than that of cyclosporine. In addition, the FK506 (1 and 3 mg/kg) was found to be effective in preventing EAU even when administered only in the early induction phase (days 0-5) or late effector phase (days 7-12). Similar effects were obtained by cyclosporine at a daily dose of 30 mg/kg. Furthermore, none of the rats immunized with S-antigen and treated with FK506 (1 mg/kg) on days 0-14 developed EAU when reimmunized with S-antigen on day 30. In contrast, similarly treated rats were fully susceptible to the induction of experimental allergic encephalomyelitis, or even to EAU when immunized with another retinal antigen, interphotoreceptor retinoid-binding protein. Therefore, as with cyclosporine, as demonstrated in our previous study, FK506 has the capacity to induce immunological unresponsiveness specific to the S-antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of a new immunosuppressive agent, FK506, on experimental autoimmune uveoretinitis in rats. 245 29

We investigated the effect of a new immunosuppressant, FK506, on the development of experimental allergic encephalomyelitis (EAE) in rats. EAE developed in 100% of rats immunized with myelin basic protein (MBP) in complete Freund's adjuvant. FK506 in doses of 1.0 mg/kg/day or more prevented the clinical signs of EAE for at least 50 days, when administered intramuscularly 5 days a week for 2 weeks starting on the day of immunization (days 0-4 and days 7-11), and a similar result was obtained, when the compound was given for 5 days (days 0-4). FK506, however, showed a significant but weak effectiveness when started from 7 days after immunization. Delayed-type hypersensitivity (DTH) to MBP developed before EAE, and anti-MBP antibody levels increased. Both humoral and cellular immune response to MBP were completely suppressed in rats treated with FK506. From these results, it is presumed that immunosuppression of cell-mediated immunity and/or humoral immunity by the treatment of FK506 actually causes the decreased incidence noted in the experiment for the development of EAE.
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PMID:Immunosuppressive effect of FK506 on experimental allergic encephalomyelitis in rats. 246 74

We reviewed retrospectively the clinical records, autopsy protocols and central nervous system tissue sections of 50 patients who underwent orthotopic liver transplantation for end-stage liver disease between 12/83 and 8/93. The postoperative survival period ranged from hours (6), weeks (17), months (17), to years (10). All patients received immunosuppressive drugs from the immediate postoperative period to the time of their death (cyclosporine, steroids; occasionally azathioprine, OKT3, FK506). Nineteen patients had neurological manifestations (hepatic encephalopathy) prior to surgery. Post-transplant neurologic signs and symptoms included: hepatic encephalopathy/altered mental status (11), focal or generalized seizures (9) and stroke (2). In the majority of cases (37) the cause of death was septicemia and/or bleeding diathesis. The neuropathologic findings present in 36 patients could be classified into 3 distinct categories: metabolic disorders: hepatic/anoxic encephalopathy, central pontine myelinolysis (15); cerebrovascular disease: subarachnoid and/or intracerebral hemorrhage, bland or hemorrhagic infarction (23); and infection: bacterial meningitis/cerebritis, multifocal fungal microabscesses, presumptive viral meningitis/encephalomyelitis (10). In conclusion, 72% of 50 patients who came to autopsy after liver transplantation were found to have neuropathologic abnormalities; these abnormalities were predominantly infections and vascular diseases.
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PMID:Neuropathology of liver transplantation. 760 96

The effect of the immunosuppressive drug FK 506 on encephalomyelitis (EAE) in Lewis rats was studied. Treatment that began during EAE induction delayed EAE onset, but when the disease started it was chronic/progressive and of unusual severity and duration, leading to death in many animals. Treatment started after onset of EAE shortened the disease. Forty seven days after immunization, extensive demyelination and inflammation were observed in the spinal cords of rats treated with FK 506 from the day of EAE induction. Rats treated after EAE onset had only minimal pathological abnormalities.
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PMID:Immunoaugmenting effect of FK 506 on experimental allergic encephalomyelitis in Lewis rats. 977 10

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) in which demyelination and axonal loss result in permanent neurologic disability. We examined the neuroprotective property of the immunosuppressant FK506 (tacrolimus), FK1706 (a nonimmunosuppressant FK506 derivative) and cyclosporin A (CsA) in a chronic relapsing experimental autoimmune encephalomyelitis (EAE) model of MS. Female SJL/J mice were immunized by subcutaneous (s.c.) injection with proteolipid protein 139-151 peptide in complete Freund's adjuvant. At the onset of paralysis, 12-14 days after immunization, mice received daily s.c. injections of FK506 (0.2, 1, and 5 mg/kg), FK1706 (5 mg/kg), CsA (2, 10, and 50 mg/kg), saline or vehicle (30% dimethylsulfoxide) for 30 days. FK506 (at a dose of 5 mg/kg) reduced the severity of the initial disease and suppressed relapses. FK1706 did not significantly alter the clinical course and CsA (at a dose of 50 mg/kg) lessened the severity of the initial episode of EAE but did not alter relapses. In the thoracic spinal cord, FK506 (5 mg/kg), FK1706 (5 mg/kg), and CsA (50 mg/kg) significantly (P < 0.001) reduced the extent of damage in the dorsal, lateral, and ventral white matter by a mean of up to 95, 68, and 30%, respectively. A nonimmunosuppressant dose of FK506 (0.2 mg/kg) also significantly (P < 0.001) reduced the extent of damage in the spinal cord by a mean of up to 45%. Other dosages of these compounds were ineffective. FK506 markedly protects against demyelination and axonal loss in this MS model through immunosuppression and neuroprotection.
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PMID:FK506 and a nonimmunosuppressant derivative reduce axonal and myelin damage in experimental autoimmune encephalomyelitis: neuroimmunophilin ligand-mediated neuroprotection in a model of multiple sclerosis. 1524 93

Accumulating data indicate that vitamin D, a sun-induced hormone, plays a key role in multiple sclerosis (MS) etiology. Notably, it has been shown that there is a remarkable season of birth effect in MS. We surmised that gestational vitamin D deficiency is a risk factor for MS. To test this hypothesis, a vitamin D deficiency was induced in C57BL/6 female mice 6 weeks prior to conception and prolonged until offspring birth. Contrary to our prediction, we show here that adult offspring exposed to developmental vitamin D deficiency (DVD) developed a striking milder and delayed experimental autoimmune encephalomyelitis (EAE), when compared to control offspring. Using reverse transcription and quantitative real-time PCR, we measured the expression level of 22 candidate transcripts in the spleen, the cerebrum and the spinal cord, at Day0 and Day30 post-immunization. We report here that, at Day30 post-immunization, TNF, osteopontin, H2-Eb were over-expressed and IFN was under-expressed in the spinal cord of control mice and not in DVD mice. Another discrepancy between nervous and immune systems was observed: expression of IL4 was dysregulated exclusively in the spleen. Reduced symptom severity in DVD mice can partially be explained by a nervous system-restricted over-expression of vitamin D receptor (VDR), two heat shock proteins (HSP90, HSPa8) and FK506 binding protein 1a (FKBP1a), at Day0. Our clinical test and molecular findings converge to indicate that maternal hypovitaminosis D imprints the foetus and alters the susceptibility of the offspring to EAE. We propose a new hypothesis to explain our unexpected observations.
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PMID:Severity of experimental autoimmune encephalomyelitis is unexpectedly reduced in mice born to vitamin D-deficient mothers. 2021 84

Multiple sclerosis (MS) is a T-lymphocyte-mediated autoimmune disease that is characterized by inflammation in the central nervous system (CNS). Although many disease-modifying therapies (DMTs) are presumed effective in patients with MS, studies on the efficacy and safety of DMTs for preventing MS relapse are limited. Therefore, we tested the immunosuppressive anti-inflammatory effects of oral-formulated tacrolimus (FK506) on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE). The mice were randomly divided into 3 experimental groups: an untreated EAE group, a low-dose tacrolimus-treated EAE group, and a high-dose tacrolimus-treated EAE group. After autoimmunization of the EAE mice with myelin oligodendrocyte glycoprotein, symptom severity scores, immunohistochemistry of the myelination of the spinal cord, and western blotting were used to evaluate the EAE mice. After the autoimmunization, the symptom scores of each EAE group significantly differed at times. The group treated with the larger tacrolimus dose had the lowest symptom scores. The tacrolimus-treated EAE groups exhibited less demyelination and inflammation and weak immunoreactivity for all of the immunization biomarkers. Our results revealed that oral-formulated tacrolimus inhibited the autoimmunization in MS pathogenesis by inactivating inflammatory cells.
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PMID:The Anti-Inflammatory Effects of Oral-Formulated Tacrolimus in Mice with Experimental Autoimmune Encephalomyelitis. 2877 47

We present a case of a 65-year-old African American male, immunosuppressed on Tacrolimus, who initially presented with cerebellar ataxia and rapidly developed Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM) with positive anti-glutamic acid decarboxylase (GAD65) antibodies, no underlying malignancy, and normal neuroimaging. PERM is a rare spectrum of Stiff Person Syndrome (SPS), which is strongly associated with anti-GAD antibodies and characterized by flare-ups and remissions of encephalopathy, myelopathy and rigidity with myoclonus. PERM is diagnosed clinically and has been successfully treated with both Intravenous Immunoglobulin (IVIg) and plasmapheresis. Our patient was successfully treated with IVIg. On day 14 after starting IVIg treatment, his neurological symptoms started to improve and ultimately returned to baseline.
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PMID:Anti-glutamic acid decarboxylase (GAD) positive cerebellar Ataxia with transitioning to progressive encephalomyelitis with rigidity and myoclonus (PERM), responsive to immunotherapy: A case report and review of literature. 3101 81


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