Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of thoracic duct lymph drainage (5-34 days) in 12 patients with myasthenia gravis on muscular function has been followed for 5-43 months. Among the results obtained were: (1) During the drainage the myasthenic symptoms decreased markedly after 1-4 days and remained so during the drainage. (2) The doses of cholinesterase inhibitors had to be markedly reduced during the lymph drainage in eight patients. (3) Discontinuation of the lymph drainage increased the myasthenic symptoms within a few days. However, after a median observation time of 14 months with conventional treatment all but one of the patients had improved. (4) Retransfusion of the patients own cell-free lymph caused a worsening of the myasthenic symptoms. This effect could also be obtained following infusion of IgG preparations from the patients lymph. Three retransfusions of cell suspensions obtained from the thoracic duct lymph from two patients had no effects on their myasthenic symptoms. (5) It is suggested that thoracic duct lymph drainage can be combined with other forms of treatment in severe cases of myasthenia gravis.
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PMID:Drainage of thoracic duct lymph in twelve patients with myasthenia gravis. 16 80

Rabbits injected with purified acetylcholine (ACh) receptor protein produce antibodies against the receptor and develop generalized muscle weakness. The compound muscle action potentials show a decremental fall in amplitude with repetitive nerve stimulation. Both the weakness and the decrement is counteracted by reversible cholinesterase inhibitors. Intracellular recordings from muscle endplates show that the amplitude of the miniature end-plate potentials is considerably reduced. A reduced binding of neurotoxin to muscles from immunized rabbits was observed. Nerve impulses release a normal number of ACh packages (quanta) from the motor nerve terminals. The muscle weakness in immunized rabbits thus has the same features as the muscle weakness in myasthenia gravis and may be a good animal model of myasthenia gravis.
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PMID:Acetylcholine receptor protein. Neuromuscular transmission in immunized rabbits. 18 5

We studied a 57-year old woman with severe myasthenic syndrome predominantly proximal. There was no therapeutic effect using cholinesterase inhibitors. Clinical findings, electromyography, whole body scanning and biopsy revealed polymyositis. Thirteen years before the patient was operated of a benign thymoma. The history of the patient showed numerous life threatening episodes of viral and fungal infections. Autoimmune anemia was diagnosed. Investigations of the immune system in vivo and in vitro revealed severe qualitative and quantitative defects in the lymphocyte population spontaneously forming rosettes with sheep red blood cells (SRBC). Thymoma, autoimmune disorder, such as polymyositis and myasthenia gravis, unspecifically elevated antibody titers, multiple severe viral and fungal infections and the defect of the cell-mediated immunity suggest a T-lymphocyte effector- and regulatory dysfunction in this patient.
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PMID:Polymyositis, myasthenic syndrome and thymoma in a patient with defective cell-mediated immunity. 31 78

Myasthenia gravis developed in two children at 2 and 3 years of age respectively. Minimal improvement followed chronic oral administration of cholinesterase inhibitors. Patient 1 had ptosis and ophthalmoplegia but no clinical or electromyographic involvement of muscles of the extremities, although a quadriceps muscle biopsy revealed lymphorrhages. Patient 2 had progressive generalized myasthenia for 3 1/2 years. Both children were given a 3-month course of prednisone followed by thymectomy. They both are in remission, 12 and 8 months after thymectomy, with only minimal residual ocular weakness, but this weakness is much more responsive to anticholinesterase drugs than before thymectomy. Long-term administration of steroids, with the attendant complication of growth retardation, is avoided.
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PMID:Effective treatment of infantile myasthenia gravis by combined prednisone and thymectomy. 55 63

The acetylcholine receptors at the mammalian motor end plate have been counted and their distribution there determined ultrastructurally. Electron microscope autoradiography applied to muscles labeled with alpha-(3H)bungarotoxin was used for this purpose. The receptors are distributed asymmetrically along the postsynaptic membrane, being concentrated at the fold crests-that portion nearest to the presynaptic membrane. The density of receptor sites at that region is estimated to be 20,000-25,000 per mum2 of membrane surface. This density holds for the several species and muscle types thus far examined and appears to be a constant parameter of the motor end plate. It determines the limit of responsiveness to acetylcholine. By contrast, the enzyme acetylcholinesterase is found to be distributed evenly over the folds and may reside in the intersynaptic matrix. When mouse diaphragm end plates from dystrophic animals or animals following 5-day denervation were similarly examined, no significant alterations in either the density or the distribution of the receptor sites were found. Similarly, dystrophic muscles in chickens possess an unaltered number of receptors at their end plates. A model is outlined to correlate receptor and cholinesterase concentrations with known aspects of transmitter release. These findings may have relevance to some of the electrophysiological abnormalities seen in myasthenia gravis.
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PMID:Ultrastructural studies on the acetylcholine receptor at motor end plates of normal and pathologic muscles. 78 17

Plasmapheresis combined with prednisone and azathioprine therapy produced striking clinical improvement in five patients with myasthenia gravis who still had moderate to severe disability despite thymectomy, high-dose prednisone therapy and optimal doses of cholinesterase inhibitors. Serial determinations of titers of serum antibody toward the acetylcholine receptor demonstrated a fall to 21 +/- 5 per cent (mean +/- S.D.) of the original levels concurrently with the patients' increasing strength. Clinically improved patients maintained lowered titers, whereas clinical relapses were associated with a rebound in titer. Our results suggest that plasmapheresis will find a place in the management of patients with myasthenia gravis, and they implicate antibodies to acetylcholine receptor as a pathogenic factor in this disease.
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PMID:Plasmapheresis and immunosuppressive drug therapy in myasthenia gravis. 91 42

The morphology of motor end-plates in rabbits immunized with Torpedo nicotinic acetylcholine receptor (nAChR) has been studied by light and electron microscopy. Rabbits were studied either after one period of paralysis, some in parallel with electrophysiological recordings of MEPPs and EPPs and of Naja naja alpha-neurotoxin binding properties or after recovery followed by a second paralysis. Changes in the sub-neural apparatus were noted after cholinesterase staining only in the latter group. Ultrastructurally, however, most end-plates in both groups contained a wide range of abnormalities. Many were similar in appearance to those observed in human myasthenia gravis (MG). This further supports the theory that immunized rabbits can be used as a model for myasthenia gravis. In the rabbits with 1 period of paralysis an acute stage of influence on the neuromuscular junction seemed to be present while simplified motor end-plates typical for human MG were mostly found in rabbits with 2 periods of paralysis. Short post-synaptic folds in conjugation with thickeneed membrane-bound vesicles at their tops, inside the basement membrane, were frequently observed. These were interpreted as if the crests of the folds containing nAChR had degenerated and had been budded off. If so, a large number of receptor sites had been lost which would be one possible explanation for the lowered capacity of the muscles to bind Naja naja alpha-neurotoxin. Membrane thickenings with projections and striations were interpreted as reflecting ACh receptors and were observed in the post-junctional membrane without proximity to the nerve terminal. The degeneration of the top of the post-synaptic folds and the occurrence of receptors at other locations within the motor end-plate will result in a widened distance between the nerve terminal and the receptors, which can explain previous interpretations of a presynaptic defect in MG.
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PMID:Morphological observations on motor end-plates in rabbits with experimental myasthenia. 97 17

Based on 60 of our own cases and on the medical literature the authors discuss the diagnostic, pathophysiological and therapeutic aspects of myasthenia gravis. Myasthenia is suspected in cases of motor weakness of changing intensity, diminishing by rest. The weak muscles are innervated by different peripheral nerves. At the beginning a weakness of upperlid-muscles, external eye muscles and bulbar muscles is particularly frequent. There is no sensory loss or other neurological symptoms. A transitory disappearance of motor weakness after an intravenous dose of Edrophonium (Tensilon) is a typical diagnostic sign. The effect is less evident with eye-muscle weakness. A typical appearance of potentials after repetitive stimulation of peripheral nerves as well as other characteristics in electrophysiological testing of muscles are of high diagnostic value. This allows differentiation from other types of muscle weakness. In the pathogenesis of myasthenia an autoimmune process related to a persistent thymus gland plays an important part. This leads to an ultrastructural change in the postsynaptic membrane of the muscle fibre. The postsynaptic membrane no longer reacts in a normal way to acetylcholine as a transmitter substance at the level of the motor endplate. Therefore the first step in the treatment of myasthenia consists of cholinesterase-inhibitors, specially Neostigmin (Prostigmin) and Pyridostigmin (Mestinon). Thymectomy is advised in all cases of myasthenia with the exception of the pure ocular form and of myasthenia in patients older than 60 years. The thymus gland is practically always persistent or hypertrophic in myasthenia. The suprasternal access is recommended. A thymoma should always be operated upon because of the danger of malignancy. In cases where thymectomy is not performed or not successful and if cholinesterase-inhibitors are not sufficiently efficient, treatment with corticosteroids or ACTH is recommended.
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PMID:[Pseudoparalytic myasthenia gravis. Diagnostic and therapeutic aspects in 60 separate cases]. 98 76

The course in 58 cases of myasthenia gravis in subjects over 50 years of age is reported. They total about 30% of cases in all age-groups. 36.2% of the patients died after an average period of illness of 3.4 years. 58.6% initially showed only ocular symptoms and in 58.8% of these the myasthenia was likewise located only in the eyes in the further course of the illness. The prognosis of ocular myasthenia is very good if the myasthenic process does not extend to other muscle groups in the first or second year of illness. 41.2% of primary ocular myasthenia turned into other types, in most cases a generalized type, and these had a poor prognosis. 69.2% of these patients died after an average period of illness of 1.5 years due to myasthenia-induced complications. Cases of myasthenia which initially are of the generalized type, in which the average duration is only 2.7 years until death, and to some extent the bulbar types, also have a poor prognosis. Ocular myasthenic cases generally need only small doses of cholinesterase inhibitors. Some patients had no medical treatment because there was no subjective or objective need for it. Several patients were given doses of cholinesterase inhibitors which were too large; excessive doses are to be avoided because of the proven negative influence of cholinesterase inhibitors on the myoneural system. It is recommended that types of myasthenia with a poor prognosis be treated early with corticoids, ACTH or azathioprin, if the cholinesterase inhibitors have proved ineffective or it their effect is unsatisfactory. Thymectomy is advisable only in patients under 60 years of age.
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PMID:[Myasthenia gravis in old age. A retrospective study of 58 patients]. 99 21

The present series of thirty patients has led us to certain conclusions concerning the management and treatment of patients with myasthenia gravis. The use of cholinesterase inhibitors alone is reserved for those patients with purely ocular myasthenia whose deficits can be satisfactorily corrected with those agents. Some of those with ocular involvement may be disabled; and in light of our excellent results with that small group, as well as similar findings presented by Fischer et al., patients with disabling or refractory ocular myasthenia should be considered for treatment with prednisone. All other patients with myasthenia are given a course of oral corticosteroids (prednisone) initially at high doses, with subsequent tapering to maintenance, alternate-day low-dose therapy. Cholinesterase inhibitors are used as needed while the patient is receiving corticosteroids. We now anticipate that patients will exhibit sustained improvement within the first two weeks, reaching maximal improvement at about three months. Exacerbations of myasthenic weakness may occur in the early phases of treatment. Such exacerbations have been commonly mild and occur with a mean onset at 5 days, and have a mean duration of 6 days. Most patients have been able to tolerate an alternate-day schedule of prednisone therapy when maintenance levels were achieved. The effective maintenance dose has been determined as the smallest dose of prednisone which allows the patient to maintain maximal improvement. Following the establishment of maximal improvement, patients have been considered for thymectomy. In our experience, the sternum-splitting procedure has been tolerated extremely well by patients exhibiting marked imporvement or remission while on corticosteroids. In those patients where thymectomy is contraindicated, irradiation of the thymus might be considered. Patients are continued on maintenance steroid therapy following surgery for a period of time that has been arbitrary. Currently, we consider an attempt to discontinue steroids at approximately one year reasonable. Should the patient relapse after discontinuation of the medication, oral corticosteroid treatment is reinitiated. Consideration is given to the possibility of recurrent thymus in patients who repeatedly fail to maintain a remission when steroids have been stopped. Our experience has not permitted us to draw firm conclusions concerning how long a time high-dose daily steroid treatment should be continued in patients who show no favorable response to that therapy. Other modes of treatment, such as courses of parenteral ACTH, methyl prednisolone, dexamethazone, or antimetabolites might be considered if there is no response after 12 weeks of high-dose, daily corticosteroid therapy.
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PMID:Long-term prednisone followed by thymectomy in myasthenia gravis. 106 98


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