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)

During a 42-month period, we used plasmapheresis to treat four cases of myasthenia gravis with refractory respiratory failure. All four patients were ventilator dependent for prolonged periods and were not responding to management with cholinesterase inhibitors and corticosteroids. All four patients rapidly responded to the plasmapheresis; respiratory muscle strength returned sufficiently to allow discontinuation of assisted mechanical ventilation and removal of the artificial airway. In our experience, plasmapheresis is indicated in the treatment of the myasthenia gravis patient with respiratory failure which is refractory to conventional drug therapy.
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PMID:Plasmapheresis in the treatment of ventilator-dependent myasthenia gravis patients. Report of four cases. 672 82

In 13 Smooth Fox Terriers with a congenital form of myasthenia gravis, clinical signs included intermittent, progressive muscle weakness that became more pronounced with exercise; muscle wasting; megaesophagus; and aspiration pneumonia. Neurologic abnormalities were apparent only during periods of weakness and included inability to retract the fore- and hindlimbs from painful stimuli. A decrement of the compound muscle action potential was evident during repetitive supramaximal nerve stimulation. Intravenous injection of a short-acting cholinesterase inhibitor evoked immediate improvement of clinical and electromyographic signs. Intracellular microelectrode studies of a biopsied external intercostal muscle revealed reduced amplitude of miniature end-plate potentials, as occurs in acquired myasthenia gravis. However, in contrast to acquired myasthenia gravis, antibodies directed against acetylcholine receptors were not demonstrable in serum and were not bound to acetylcholine receptors in muscle. Despite lack of complexing with immunoglobulin, the amount of acetylcholine receptor protein in biopsied external intercostal muscles from 9 affected pups was less than 25% of the amount in 5 unaffected littermates. The latter finding accounted for the reduction in amplitude of miniature end-plate potential and the failure of neuromuscular transmission. Treatment with a long-acting cholinesterase inhibitor in 6 cases resulted in temporary improvement in muscle strength.
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PMID:Congenital myasthenia gravis in 13 smooth fox terriers. 684 Dec 51

At the normal mammalian neuromuscular junction the half-life of the acetylcholine receptor (AChR) ranges from 6 to 13 days (estimates from seven different laboratories). Indirect evidence suggests that the internalized receptor is degraded by a lysosomal mechanism. We have now traced the fate of the AChR labelled in vivo with peroxidase-alpha-bungarotoxin. Segments of junctional folds bearing AChRs are internalized by endocytosis. The endocytosed vesicles are engulfed by tubules and larger vesicles which, by electron cytochemical criteria, represent secondary lysosomes. Pathological mechanisms increased AChR loss from the end-plate. These include destruction of junctional folds, formation of immature junctions with a few or no junctional folds, accelerated internalization of AChR, impaired membrane insertion of new AChR and, possibly decreased AChR synthesis. The common mechanism for destruction of the junctional folds is an altered subsynaptic ionic milieu, and especially focal calcium excess. This can be induced by antibody and complement, too frequent or prolonged openings of the acetylcholine (ACh)-induced ion channel, and other membrane defects. In acquired autoimmune myasthenia gravis there is (a) antibody-dependent complement-mediated lysis of the junctional folds, (b) accelerated internalization of AChR cross-linked by antibody and (c) decreased insertion of AChR into the postsynaptic membrane. The last mechanism is attributed to lack of membrane patches available for tight packing and secure anchoring of the receptor. In acute, but not in chronic, experimental autoimmune myasthenia gravis, and infrequently in human myasthenia gravis, macrophages destroy junctional folds opsonized by antibody and C3. In a recently recognized congenital syndrome attributed to a prolonged open time of the ACh-induced ion channel, and to a lesser extent in congenital end-plate acetylcholinesterase deficiency, AChR is lost with degradation of junctional folds. In other, less well-defined, congenital syndromes there is deficiency or abnormal function of AChR. This could arise from decreased synthesis or membrane insertion or accelerated degradation of AChR, or from a structurally abnormal AChR with reduced affinity for ACh or with a diminished conductance or open time of its ion channel.
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PMID:Mechanisms of acetylcholine receptor loss from the neuromuscular junction. 692 8

Myasthenia gravis is a neuromuscular disease that presents clinically as fluctuating weakness of one or more skeletal muscle groups. Weakness becomes more severe with exercise and improves with rest. The disease is caused by an autoimmune reaction at or near the post-synaptic nicotinic acetylcholine receptor. The results of this immune reaction are the lytic destruction of the post-synaptic membrane and a reduction in the number of acetylcholine receptors. Myasthenia gravis can be diagnosed by repetitive exercise of the involved muscles, administration of edrophonium (Tensilon), electrophysiologic testing, or demonstration of anti-acetylcholine receptor antibodies. When the myasthenic weakness is mild or limited to the extraocular muscles, it may be treated with acetylcholinesterase inhibitors. When the weakness is more severe and/or more generalized, immunotherapy is most often indicated. Prednisone or prednisone plus thymectomy is the most frequently used form of immunotherapy. Azathioprine, 6-mercaptopurine, plasmapheresis, or gamma globulin injections are other immunotherapeutic options that may be useful in selected patients. A large number of drugs may precipitate or exacerbate myasthenic weakness.
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PMID:Myasthenia gravis: signs, symptoms, diagnosis, immunology, and current therapy. 692 2

Over a 10-year period 12,643 gynecologic surgical procedures were performed with the patients under general anesthesia. Succinylcholine was the muscle relaxant used in the majority of cases. Four of these patients developed prolonged postoperative apnea; the longest period of apnea was 6 hours. In one patient atypical cholinesterase was documented, and two of the patients were subsequently diagnosed as having myasthenia gravis. In the fourth case an etiology for the apnea was not demonstrated. A compilation of drugs in common clinical usage which interfere with neuromuscular transmission is included.
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PMID:Prolonged postoperative apnea complicating gynecologic surgery; atypical cholinesterase and myasthenia gravis. 708 10

Myasthenia gravis is characterized by variable ocular and skeletal muscle weakness. Peak incidence is in young women and older men. Thymomas are present in 30 percent of myasthenic patients over age 40. Binding of acetylcholine receptors by IgG antibodies may be the mechanism of the neuromuscular disorder. Repetitive nerve stimulation (Jolly test), provocative tests with quinine or curare and the edrophonium test (cholinesterase inhibition) are the diagnostic maneuvers employed.
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PMID:The neuromuscular junction. Part II: myasthenia gravis. 745 20

We report on a case of reversible pontine deafness caused by multiple sclerotic lesions in the pons, and describe six experiments in humans, in whom we recorded transient otoacoustic emissions and distortion products. Our findings indicate an inhibitory effect of efferent innervation on the motility of outer hair cells in humans. Otoacoustic emissions increased in patients with unilateral deafness after the central part of the efferent pathway was destroyed (pontine deafness). Otoacoustic emissions also increased in patients with myasthenia gravis after the administration of an acetylcholinesterase inhibitor. General myotonia (Batter-Curschmann-Steinert Syndrome) resulted in mild sensorineural hearing loss, and in the absence of contralateral inhibition of otoacoustic emissions. Otoacoustic emissions decreased gradually under general anesthesia with muscle relaxation. Contralateral acoustic stimulation was seen during anaesthesia with muscle relaxation.
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PMID:The efferent innervation of outer hair cells in humans: physiological investigations. 761 Aug 6

A patient developed a severe cholinergic syndrome from the use of echothiophate iodide ophthalmic drops, presented with profound muscle weakness and was initially given the diagnosis of myasthenia gravis. Red blood cell and serum cholinesterase levels were severely depressed and symptoms resolved spontaneously following discontinuation of the eye drops.
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PMID:Cholinergic toxicity resulting from ocular instillation of echothiophate iodide eye drops. 765 Jul 71

Cholinesterases form a family of serine esterases that arise in animals from at least two distinct genes. Multiple forms of these enzymes can be precisely localized and regulated by alternative mRNA splicing and by co- or posttranslational modifications. The high catalytic efficiency of the cholinesterases is quelled by certain very selective reversible and irreversible inhibitors. Owing largely to the important role of acetylcholine hydrolysis in neurotransmission, cholinesterase and its inhibitors have been studied extensively in vivo. In parallel, there has emerged an equally impressive enzyme chemistry literature. Cholinesterase inhibitors are used widely as pesticides; in this regard the compounds are beneficial with concomitant health risks. Poisoning by such compounds can result in an acute but usually manageable medical crisis and may damage the CNS and the PNS, as well as cardiac and skeletal muscle tissue. Some inhibitors have been useful for the treatment of glaucoma and myasthenia gravis, and others are in clinical trials as therapy for Alzheimer's dementia. Concurrently, the most potent inhibitors have been developed as highly toxic chemical warfare agents. We review treatments and sequelae of exposure to selected anticholinesterases, especially organophosphorus compounds and carbamates, as they relate to recent progress in enzyme chemistry.
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PMID:Anticholinesterases: medical applications of neurochemical principles. 772 78

In the present study we analysed by ELISA the ability of sera from 50 patients with myasthenia gravis (MG), 20 with Hashimoto's thyroiditis (HT), 53 with Graves' disease (GD) and 36 healthy controls (CR) to react with acetylcholinesterase (AChE) from Electrophorus electricus and human thyroglobulin (Tg). Significantly increased anti-AChE activity was exhibited by a high proportion of MG (IgG 36%) and GD (IgG 21%) sera, while increased anti-Tg activity was detected in all three patient groups (MG, IgG 26% and IgA 26%; HT, IgG 85% and IgA 40%; and GD, IgG 51%). Interestingly, a significant proportion of MG and GD sera exhibited both IgG anti-AChE and anti-Tg activities (MG, 18%; P < 0.001; and GD, 15%; P < 0.001, versus CR, 0%). This bi-reactivity was exhibited by anti-AChE antibodies cross-reacting with Tg (anti-AChE/Tg activity); (i) serum anti-AChE activity was effectively inhibited by soluble Tg, and (ii) affinity-purified anti-Tg antibodies cross-reacted with AChE. Cross-reactivity seems to be a property of pathological (auto)antibodies; induced (rabbit) antibodies to AChE or Tg were highly monospecific. Analysis of clinical data showed that increased IgG anti-AChE/Tg activity was well associated with: (i) overlapping GD in MG (P < 0.02), and (ii) ophthalmopathy in GD (P < 0.01). In contrast, no correlation was noted in MG between anti-AChE activity units and anti-Tg activity units or acetylcholine receptor antibody titres. The clinical significance of anti-AChE/Tg antibodies remains to be elucidated.
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PMID:Antibodies to acetylcholinesterase cross-reacting with thyroglobulin in myasthenia gravis and Graves's disease. 774 74


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