Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adult, acquired, idiopathic, autoimmune myasthenia gravis has a well-characterized IgG anti-acetylcholine striated-muscle receptor antibody. Removal by plasma exchange is effective, established therapy to augment anti-cholinesterase and immunosuppressive therapy and is the treatment of choice for myasthenia gravis crisis. We report 36 consecutive patients referred and accepted for plasma exchange, 32 of whom were in or entering myasthenia crisis, over a 10 year period. An average of 7.8 (range 1 to 16) plasma exchange procedures were done, with uniform, significant improvement, including extubation of 13 in myasthenic crisis and discharge from hospital in all. We conclude that this is the best treatment for myasthenia gravis crisis in hospital. From recent cases, most, if not all, crises can be prevented by IVIgG or plasma exchange as out-patients with use of corticosteroid and or azathioprine.
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PMID:Predictable recovery from myasthenia gravis crisis with plasma exchange: thirty-six cases and review of current management. 1035 56

Myasthenia gravis is caused by an autoimmune attack to acetylcholine receptors of skeletal muscle. Acetylcholine release from motor nerve terminals is upregulated in patients with myasthenia gravis and also in rat "myasthenic" models, dependent on the reduction of the number of acetylcholine receptors. This study addresses the question as to whether at "myasthenic" endplates there are changes in the activity of acetylcholinesterase. To this end we studied acetylcholinesterase activity in junctional and extrajunctional regions of dilator naris, extensor digitorum longus, and hemidiaphragm muscles from rats with alpha-bungarotoxin-induced myasthenia gravis. In all studied muscles from "myasthenic" rats there was no significant change of junctional acetylcholinesterase activity. In contrast, in dilator naris and extensor digitorum longus muscles, there was a 60% and 30% increase of extrajunctional acetylcholinesterase activity. There was no significant change in the extrajunctional activity in hemidiaphragm muscles. Velocity sedimentation analysis revealed that the increase in extrajunctional activity in extensor digitorum longus muscles could be attributed to an increase of the activity of the G4 form of acetylcholinesterase. Treatment of rats with 6.4 microgh(-1) neostigmine bromide for 29 days had no influence on junctional and extrajunctional acetylcholinesterase activity of extensor digitorum longus muscles from rats with alpha-bungarotoxin-induced myasthenia gravis.
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PMID:Acetylcholinesterase activity of skeletal muscle in a non-immunogenic model for myasthenia gravis in rats. 1044 48

We reported a 63-year-old woman, suffered from myasthenia gravis with thymoma who later developed subacute motor neuronopathy after thymectomy. She noticed distally dominant muscle weakness and atrophy of bilateral upper extremities without sensory loss 4 month after thymomectomy. Her muscle weakness did not improve by intravenous administration of anti-cholinesterase (Tensilon test). Electrophysiological examinations showed no decremental response of examined muscles during repetitive nerve stimulation, nor motor nerve conduction block nor demyelination of affected peripheral nerves. Laboratory study demonstrated positive anti-acetylcholine receptor, anti-nuclear and SS-A antibodies. On immunohistochemistry, the patient's sera positively stained human and rat anterior horn cell cytoplasm as well as axoplasm of spinal white matter and root nerve axon, suggesting the presence of anti-axon antibody, possibly against neurofilament or tubulin components. The biopsied muscle specimen showed neurogenic muscle changes, but with no evidence of vasculitis nor cellular infiltration. Therapeutic trial of plasmapheresis was effective for her muscle weakness. Further recovery of weakness and muscle atrophy of hand muscles was obtained by combined therapy of intravenous and oral corticosteroid administration and plasmapheresis. These clinical, electrophysiological and histological findings suggested that antibodies against neuronal component might be responsible for her motor neuronopathy associated with myasthenia gravis. The findings of our case study may support the idea that some cases of motor neuron disease are caused by auto-immune mechanism.
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PMID:[Subacute motor neuronopathy associated with myasthenia gravis and thymoma]. 1054 13

Ocular symptoms of 17 myasthenia gravis (MG) patients were examined by electronystagmographic registration of optokinetic nystagmus. The aim of this study was to replace the subjective methods used previously with a more reliable quantitative technique and thus assess ophthalmoplegia and diplopia, important initial symptoms in MG. Slow phase angular speed values of foveolar type optokinetic nystagmus in the horizontal plane at 10, 20 and 30 degrees/s target speed were determined. Measurements were performed before and after administration of Mestinon, a reversible cholinesterase inhibitor. Twelve healthy volunteers were examined as controls under standard conditions. Results showed significant differences between MG patients and control group. Slow-phase angular speed was significantly larger after Mestinon administration (p < 0.001). It is concluded, that the exhaustion of external ocular muscles in MG can be well characterized by the determination of the slow phase angular speed values of optokinetic nystagmus (OKN). The examination of OKN was also recommended for the evaluation of ocular symptoms in other neurological disorders.
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PMID:Electronystagmographic analysis of optokinetic nystagmus for the evaluation of ocular symptoms in myasthenia gravis. 1058 93

The authors have for the first time evaluated the basic parameters of the voice using computed voice analysis in patients with myasthenia gravis (MG). The aim of the study was to introduce an objective method suitable for the assessment of dysphonic symptoms, which predominate in bulbar, oculobulbar and generalized MG. Voice profile studies included the evaluation of the singing voice range, voice dynamics, maximum phonation time, and mean fundamental frequency and intensity during speech. The characteristic of the stroboscopic picture was also determined. Investigations were carried out before and after the intake of Mestinon, a reversible cholinesterase inhibitor, and healthy subjects were used as a control group. In MG, the voice range and dynamics are badly impaired, maximum phonation time is shortened, the mean fundamental frequency during speech is increased, while the intensity is decreased. Mestinon resulted in an improvement in all these parameters, however, they were still impaired in comparison to the control subjects. Most changes were found to be statistically significant. The authors emphasize the role of the otolaryngologist and objective phoniatric methods in the evaluation of MG and other myasthenia-like neurological diseases. The use of these methods for the assessment of phoniatric symptoms in neurological diseases is highly recommended.
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PMID:[Phoniatric studies in myasthenia gravis patients]. 1060 89

A 31-year-old female with lymphoblastic lymphoma developed myasthenia gravis (MG) 26 months after receiving an allogeneic bone marrow transplant (BMT) from an HLA-identical sister. She presented with classic symptoms and electromyographic evidence of the disorder approximately 2 weeks after electing to abruptly discontinue her immunosuppressive medications. She initially responded to steroids and acetylcholinesterase inhibitors. Her subsequent course has been characterized by episodes of moderately severe weakness that respond to intravenous immunoglobulin and prednisone. This case of post-transplant MG is only the second reported to have occurred in association with BMT for lymphoblastic lymphoma. Potential risk factors for the development of post-transplant MG are discussed including underlying hematological disorder, HLA phenotype, family history of MG, the presence of chronic GVHD, and recent cessation of immune suppression.
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PMID:Myasthenia gravis after allogeneic bone marrow transplantation for lymphoblastic lymphoma. 1062 49

Pyridostigmine bromide (PB), a reversible inhibitor of acetylcholinesterase (AChE), is used for the treatment of myasthenia gravis. PB has also been provided to military personnel for preexposure protection against potential soman release. The entry of PB into the brain is typically minimal, but recently published data in mice suggest that a brief forced swim stress increases the permeability of the blood-brain barrier to PB. From these results, PB administered under stressful conditions was proposed to induce long-lasting central cholinergic deficits, potentially explaining the neurological and neuropsychological symptoms presented by some Gulf War veterans. In undertaking to replicate these results in the Long-Evans rat, no evidence of a stress-potentiated central effect of PB, administered at doses up 5.0 mg/kg ip, was found. Three stress protocols were used: restraint, forced swim, or a combined restraint/forced swim. Wistar rats were also tested in some of the protocols to ensure that the results were generalizable across rat strains, and plasma corticosterone levels were measured to test the effectiveness of the stressors employed. In contrast to the previously reported findings in the mouse, stress significantly reduced the entry of PB into rat brain, as measured by reduced inhibition of AChE activity: a 12.5% reduction in whole brain AChE activity after treatment with 5.0 mg/kg PB under control conditions declined to 9% after stress exposure. It is apparent, therefore, that the interaction between stress and PB requires further study, and previous data should be reassessed before they are used as a basis for interpreting symptoms presented by veterans.
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PMID:Stressful manipulations that elevate corticosterone reduce blood-brain barrier permeability to pyridostigmine in the Rat. 1081 58

The acetylcholine-hydrolyzing enzyme, acetylcholinesterase, is the molecular target of approved drugs for Alzheimer's disease and myasthenia gravis. However, recent data implicate AChE splicing variants in the etiology of complex diseases such as AD and MG. Despite the large arsenal of anti-AChE drugs, therapeutic inhibitors are primarily targeted towards an active site shared by all variants. In contrast, anti-sense oligonucleotides attack unique mRNA sequences rather than tertiary protein structures. AS-ODNs thus offer a means to target gene expression in a highly discriminative manner using very low concentrations of drug. In light of the likely role(s) of specific AChE variants in various diseases affecting cholinergic neurotransmission, the potential contribution that anti-sense technology can make towards improved approaches to anti-AChE therapeutics deserves serious attention.
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PMID:Anti-sense approach to anticholinesterase therapeutics. 1090 23

Optokinetic nystagmus (OKN) eye movements of myasthenia gravis (MG) and nonmyasthenic ocular palsies, and normal subjects were examined under closed-loop and open-loop conditions. The open-loop OKN condition was achieved by adding the signal of eye-movement velocity of OKN to the computer-generated signal controlling the stimulus grating moving. The OKN was recorded by means of electromagnetic search scleral coil technique. In MG patients, the open-loop gains of OKN increased significantly after the intramuscular injection of an acetylcholinesterase inhibitor, neostigmine, while the closed-loop OKN gains were not significantly changed. Both the closed-loop and open-loop OKN gains of normal subjects and nonmyasthenic patients were not increased for the administration of neostigmine. The experimental results indicated that the open-loop OKN gain could be sensitive to reflect the changes of the function of neuromuscular junction in MG patients.
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PMID:Open-loop and closed-loop optokinetic nystagmus (OKN) in myasthenia gravis and nonmyasthenic subjects. 1103 Oct 92

Outer hair cells (OHCs) are the source of otoacoustic emissions, following a tropomyosin-miosin-dependent contraction, which are regulated by the olivocochlear bundle via the release of acetylcholine (ACh). ACh acts on ACh receptors (AChR) located on the OHC post-synaptic membrane. In myasthenia gravis (M.G.) neuromuscular transmission is reduced due to the action of AChR autoantibodies. It has previously been shown that M.G. induces a reduction in transient evoked otoacoustic emissions (TEOAEs), which is reversed after administration of a cholinesterase (AChE) inhibitor. Distortion product otoacoustic emissions (DPOAEs) were recorded before and 60 min after oral administration of 60 mg pyridostigmine bromide in 25 patients with normal hearing affected by M.G. The results were compared with those from 25 age-matched normal controls. Mean values of DPOAE amplitude in myasthenic patients were significantly (p < 0.05) lower at all frequencies before drug administration. All patients showed an overall significant (p < 0.05) increase in DPOAE amplitude after drug administration, although without reaching the control values. Such a recovery was more evident and highly significant (p < 0.01) for middle and high frequencies and could be explained by a higher concentration of ACh receptors in the basal and middle cochlear turns. These data seem to confirm the role of ACh in the neurotransmission of the auditory efferent system and may represent a new in vivo model for the investigation of the physiology of this system.
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PMID:The role of cholinergic transmission in outer hair cell functioning evaluated by distortion product otoacoustic emissions in myasthenic patients. 1134 60


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