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 are mostly associated with small cell lung cancer. Lambert-Eaton myasthenic syndrome appears to be caused by anti-presynaptic calcium channel antibodies. Calcium channels are also present in the cell membrane of small cell lung cancer, which may trigger the formation of anti-calcium channel antibodies. It is the most convincing argument in support of the auto-immune paraneoplastic theory, which refers to cross-antigenicity. Serum of patients with small cell carcinoma and cancer-associated retinopathy contains immunoglobulins against several antigens in the retinal and tumor cells. Patients with chronic intestinal pseudoobstruction (gastrointestinal neuropathy) associated with small cell lung cancer displayed circulating IgG antibodies reactive with neurons of myenteric plexus (anti-enteric neuronal antibodies). On the other hand, high levels of anti-neuronal antibodies (anti-Hu) have been found in the serum and cerebrospinal fluid of patients suffering from subacute encephalomyelitis (limbic encephalitis, cerebellar degeneration, sensory neuronopathy) associated with small cell lung cancer. The pathogenic role of the anti-neuronal antibody is not well established. Nevertheless, the finding of high titer antineuronal antibody in patients with a suggestive clinical syndrome is of great interest since it confirms the paraneoplastic syndrome and suggests the location of the primary tumor when the cancer is unknown.
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PMID:[Autoimmunity and cancer: paraneoplastic neurological syndromes associated with small cell cancer]. 133 87

Paraneoplastic neurological syndromes are of two types: some are more often seen without than with cancers and may therefore be called "occasionally para neoplastic" (e.g. chronic sensorimotor polyneuropathy and polymyositis), while others are fairly regularly associated with cancers, and particularly with small cell lung carcinoma. In this category falls subacute encephalomyelitis, an entity of broad anatomico-clinical spectrum including limbic encephalitis and subacute sensory neuronopathy; the patient's serum and cerebrospinal fluid may contain neuronal antinuclear antibodies. One type of subacute cerebellar degeneration is characterized by the presence of antibodies specifically directed against Purkinje cell cytoplasmic antigens, and it is associated with ovarian and mammary cancers. The other type shows no antibodies or different antibodies and sometimes neuronal antinuclear antibodies; the latter case may represent the cerebellar form of subacute encephalopathy. Because it may be either a true autoimmune disease or a true paraneoplastic syndrome, Lambert-Eaton myasthenic syndrome, caused by autoantibodies that block the voltage-dependent calcium channels, stands out as the most convincing argument in support of the autoimmune paraneoplastic syndrome theory. The theory, which refers to cross-antigenicity, cannot be extended to the other syndromes without reservation: there is no evidence that autoantibodies are neurotoxic, and specific autoantibodies in high levels are sometimes detected in patients with cancer but without any neurological symptom. Nevertheless, the finding of circulating antineuronal antibodies in patients with a suggestive clinical syndrome should prompt investigations for cancer perhaps at an early stage.
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PMID:[Paraneoplastic neurologic syndromes]. 182 23

The calcium and phospholipid-binding proteins lipocortins 1, 2 and 5 have been detected, by electrotransfer and immunoblotting techniques, in central nervous system (CNS) tissues of control Lewis rats and animals with experimental allergic encephalomyelitis (EAE). The cerebellum and spinal cord content of lipocortins 2 and 5 remained unchanged throughout the development of EAE but the amounts of the steroid-inducible protein lipocortin 1 increased in samples from pre-diseased and adjuvant-treated rats and were further enhanced in tissues from clinically sick and convalescent animals. The significance of these findings is discussed in conjunction with the ongoing changes in pathology which occur during the progression of EAE.
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PMID:The detection of lipocortins 1, 2 and 5 in central nervous system tissues from Lewis rats with acute experimental allergic encephalomyelitis. 214 19

Three aspects of the pathophysiology of experimental autoimmune encephalomyelitis (EAE) are discussed: firstly, the possible electrophysiological effects in the CNS of myelin basic protein, which is released during demyelination; secondly, the partial degeneration of monoaminergic and glutamatergic neurons which occurs during an attack of EAE in addition to demyelination; thirdly, the importance of ischemic events, accompanied by free radical release, in EAE. Especially the third aspect could have therapeutic implications. Treatment with radical scavengers, N-methyl-D-aspartate receptor blockers, or calcium blockers (as suggested for ischemia) might prove effective for EAE. Our present aim is to investigate whether these results are also relevant for MS, for which EAE is an animal model.
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PMID:Some pathophysiological aspects of experimental autoimmune encephalomyelitis. 247 88

The hormone 1 alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3) has immune modulatory activities in vitro and in vivo, and can prevent or delay the onset of experimental or spontaneous autoimmune diseases. At therapeutical doses, however, hypercalcemic side effects are found. The present experiments examined the effects of combined treatment with subtherapeutic doses of cyclosporine A (CsA) and 1,25(OH)2D3 on the evolution of experimental autoimmune encephalomyelitis (EAE) in SJL mice. 1,25(OH)2D3 at 5 micrograms/kg body weight (given by i.p. injection every 2 days) prevented the appearance of paralysis in 70% of the treated mice. The treatment with 1,25(OH)2D3 at 2 micrograms/kg/2 days alone had less substantial protective effects (22% disease-free animals versus 5% in the control group). However, when this subtherapeutic dose was associated to treatment with a daily dose of CsA (2 or 5 mg/kg/day), which by itself was subtherapeutic (24 and 50% disease-free animals, respectively), the association of both drugs led to near-total protection (86% disease-free animals when combined with the highest dose of CsA). When an alternate day administration schedule (CsA at 10 mg/kg and 1,25(OH)2D3 at 2 micrograms/kg, each given on alternate days from day -3 to +19 after disease induction) was used, all treated mice were completely protected clinically and histologically. The two drugs also showed additive effects on serum osteocalcin and urinary calcium and desoxypyridinoline excretion, but not on serum calcium concentration. Our experiments demonstrate that 1,25(OH)2D3 might be a potential dose-reducing agent for CsA in immunosuppressive therapy.
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PMID:Prevention of murine experimental allergic encephalomyelitis: cooperative effects of cyclosporine and 1 alpha, 25-(OH)2D3. 759 50

A 25-year-old man was hospitalized because of dyspnoea and retrosternal pain. There were clinical and radiological signs of severe left ventricular failure which within a few hours necessitated artificial ventilation. A year before he had been diagnosed as having pseudohyperparathyroidism and disseminated encephalomyelitis. Administration of calcium and vitamin D was only partially efficacious. On admission the calcium concentration was 1.5 mmol/l. The severe left ventricular failure did not respond adequately to the usual therapeutic measures including artificial ventilation and catecholamines. A cumulative dose of about 50 mmol calcium was administered intravenously over 10 days, but marked improvement in myocardial function already became apparent at a calcium concentration of about 1.8 mmol/l. Lasting correction of the hypocalcaemia was achieved with 0.5 g calcium three times daily by mouth and 0.5 mg/d dihydrotachysterol. After transfer to a special neurological department because of an acute attack of multiple sclerosis there was no detectable impairment of cardiac function. This case demonstrates that hypocalcaemic cardiomyopathy should be considered in the differential diagnosis of heart failure in previously well young persons who do not respond adequately to the usual treatment. Myocardial impairment is fully reversible after administration of calcium.
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PMID:[Hypocalcemic cardiomyopathy as the cause of severe left heart failure]. 792 18

Intracellular Ca2+ stores were investigated in resting and activated splenic T lymphocytes from Lewis rats. Activation was obtained either in vitro (spleen cells isolated from "naive" rats exposed to concanavalin A for 24 h) or in vivo (spleen cells from rats with fully developed symptoms of experimental allergic encephalomyelitis). In both experimental conditions several changes of Ca2+ homeostasis were observed with respect to resting lymphocytes: (1) a threefold increase of the total intracellular calcium (from 1.15 to 3.5 mmol/l); (2) a moderate increase of the pool sensitive to inositol 1,4,5-trisphosphate (IP3), investigated both in intact T lymphocytes (fura-2 and 45Ca(2+)-release techniques in cells challenged with phytohemagglutinin) and in T lymphocytes permeabilized with beta-escin (45Ca2+ release induced by saturating concentrations of IP3); and (3) the appearance of a pool released by the endoplasmic reticulum (ER) Ca2+ ATPase inhibitor thapsigargin (Tg), but insensitive to IP3, which, therefore, appears to be localized in areas of the ER devoid of the cognate receptor. The latter two findings were paralleled in activated lymphocytes by an increase of expression of ER markers, involved (calreticulin; Ca2+ ATPase) or not (protein disulfide isomerase) in the regulation of Ca2+ homeostasis. In contrast, calnexin (another ER marker) and the receptor for IP3 were increased to only a moderate extent. Finally, an enlargement of non-ER Ca2+ pools was observed in the cells pretreated with Tg in which 45Ca2+ release was induced by the Ca2+ ionophore ionomycin. Our results document structural and functional changes of intracellular Ca2+ stores which might play an important regulatory role in activated T lymphocytes.
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PMID:Intracellular Ca2+ stores of T lymphocytes: changes induced by in vitro and in vivo activation. 820 96

Vitamin D has been discovered at the beginning of this century. 7-Dehydrocholesterol is converted to vitamin D3 in the skin and after several hydroxylations it is further converted to the active hormonal form, 1 alpha,25-(OH)2D3. Vitamin D stimulates the absorption of calcium and phosphate and is an essential link in bone resorption and formation and calcium metabolism. 1 alpha,25-(OH)2D3 acts through a vitamin D receptor. These receptors are not only present in clinical target organs (kidney, gut, liver) but can also be found in a wide variety of "non-classical" tissues (keratinocytes, cells belonging to the immune system). Moreover, numerous cells (keratinocytes, macrophages) can locally synthetize or can be induced to synthetize 1 alpha,25-(OH)2D3 and these cells are responsive to its action. When these data are combined, a possible paracrine function of 1 alpha,25-(OH)2D3 can be suspected. Via this paracrine function 1 alpha,25-(OH)2D3 can suppress the cellular and humoral immunity. Based on the discovery of these effects on immune cells in vitro it became clear that 1 alpha,25-(OH)2D3 might be an interesting molecule to prevent autoimmune diseases and organ transplantation. This has already been shown in several animal models (Heymann nephritis, diabetes mellitus, experimental allergic-encephalomyelitis, lupus). 1 alpha,25-(OH)2D3 demonstrates however some side-effects (hypercalciuria, hypercalcemia, bone resorption) and for this reason 1 alpha,25-(OH)2D3-analogs are developed with dissociated effects i.e. an activity profile that allows a specific action on non-classical tissues without calcemic effects. Some chemical modifications of the side chain, A and/or CD-ring results in "superanalogs" with 10 to 100-fold more activity on cell differentiation and the immune system then 1 alpha,25-(OH)2D3 but with less calcemic activity in vivo. These biological effects can be explained by differences in pharmacokinetics (low affinity for the plasma vitamin D-binding protein and short extracellular half-life) and increased intracellular activation and gen transactivation. Preclinical research must still be done to select the most potent superanalogs and to find the exact protocols for the prevention and treatment of autoimmune diseases and rejection of transplanted organs.
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PMID:[Immune modulation by vitamin D analogs in the prevention of autoimmune diseases]. 857 69

A neurologic paraneoplastic syndrome may be the first sign of an occult and treatable cancer. Some syndromes are associated with autoantibodies against neuronal antigens. Patients with cerebellar degeneration and ovarian or breast cancer have antibodies against 34 and 62 kilodalton (kDa) proteins in Purkinje cell cytoplasm: anti-Yo antibodies. Patients with encephalomyelitis or sensory neuronopathy and small cell lung cancer have antibodies against 35-40 kDa neuronal nuclear proteins: anti-Hu antibodies. Patients with opsoclonus-myoclonus and breast cancer have antibodies against 55 and 80 kDa neuronal nuclear proteins: anti-Ri antibodies. Patients with Lambert-Eaton myasthenic syndrome and small cell lung cancer have antibodies against voltage-gated calcium channels (anti-VGCC) in motor nerve terminals. The presence of anti-neuronal antibodies strongly indicates that a neurological syndrome is paraneoplastic, and often identify the site of an occult neoplasm. However, the absence of detectable antibodies does not rule out the presence of an underlying tumour.
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PMID:[Neurologic paraneoplastic syndromes and anti-neuronal antibodies]. 863 63

Treatment of SJL mice with 400 ng Bordetella pertussis toxin (PT) either in saline or emulsified in incomplete Freund's adjuvant protected the mice against experimental autoimmune encephalomyelitis (EAE) induced 28 days later by a synthetic peptide of myelin proteolipid protein (PLP139-151) in complete Freund's adjuvant. However, treatment with a genetically inactivated pertussis toxin in which the catalytic and NAD-binding sites of the ADP-ribosyltransferase subunit were modified by site-directed mutagenesis was without effect. In vitro, lymphocyte proliferation was considerably enhanced by both the native and the inactivated toxin, at concentrations of 0.1-1 microgram/ml. However, strong inhibition of proliferation was also observed with the native toxin only, at concentrations that were two to three orders of magnitude lower than that required for the mitogenic effect (0.1-1 ng/ml). The inhibition of proliferation was detectable in the case of high-background proliferation, after stimulation with antigen (PLP139-151) or purified protein derivative of Mycobacterium tuberculosis), or with anti-CD3 monoclonal antibody, but not after stimulation with concanavalin A or phorbol esters and Ca2+ ionophore. These results suggest that the inhibitory effect of PT operates by interfering selectively with a T cell receptor-dependent signaling pathway. The biological significance of the in vitro inhibitory effect of PT was demonstrated by a considerable decrease and/or delay in the ability of lymphocytes grown with PLP139-151 and low concentrations of PT to transfer EAE to naive recipients.
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PMID:Native, but not genetically inactivated, pertussis toxin protects mice against experimental allergic encephalomyelitis. 864 Aug 62


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