Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1762617 (weakness)
 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of amniotic fluid on the binding of anti-acetylcholine receptor (anti-AChR) antibodies from myasthenia gravis (MG) patients to AChR preparations was examined by radioimmunoassay using 125I-labelled alpha-bungarotoxin. Human amniotic fluid from healthy women in their second trimester inhibited the in-vitro interaction between antibody and antigen. This finding suggests that during pregnancy there is a similar inhibitory effect in MG on the in-vivo binding of maternal anti-AChR antibodies, transferred through the placenta, to AChR at the fetal neuromuscular junction. The presence of feto-placental inhibitory factors may explain the development of transitory muscular weakness only after birth and only in the minority of the babies born to myasthenic mothers.
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PMID:Significance in neonatal myasthenia gravis of inhibitory effect of amniotic fluid on binding of antibodies to acetylcholine receptor. 9 75

Immunization of Lewis rats with acetylcholine receptor (AChR) purified from either Electrophorus electricus electric organ or syngeneic rat muscle induced experimental autoimmune myasthenia gravis (EAMG). This was demonstrated by clinical signs of weakness and by electromyographic evidence of imparied neuromuscular transmission. The amount of rat AChR required to induce an autoimmune response was comparable to the amount of eel AChR required. In vitro complexing of rat AChrR with antibody reduced its immunogenicity. Autoantibody to muscle AChR was present in serum and complexed with AChR in muscle. Antibody was not bound to the ACh binding site of AChR, since antibody-AChR complexes extracted from muscle could still bind 125I-alpha-bungarotoxin. The amount of AChR extracted from muscle of rats with EAMG was diminished. The amount of AChR and antibody-AChR complexes in muscle was measured at intervals after immunization with eel AChR. The amount of AChR decreased in rats with acute EAMG, then transiently increased to more than normal amounts during remission, and finally decreased to only about 20% of normal in rats with chronic EAMG. At least half of the AChR remaining in animals with chronic EAMG was complexed with antibody. Thus, both a decrease in amount of AChR and the formation of antibody-AChR complexes contribute to impairment of neuromuscular transmission in rats with EAMG. The possible mechanisms involved in the changes in AChR content are discussed.
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PMID:Pathological mechanisms in experimental autoimmune myasthenia gravis. I. Immunogenicity of syngeneic muscle acetylcholine receptor and quantitative extraction of receptor and antibody-receptor complexes from muscles of rats with experimental automimmune myasthenia gravis. 18 96

Passive transfer of experimental autoimmune myasthenia gravis (EAMG) was achieved using the gamma globulin fraction and purified IgG from sera of rats immunized with Electrophus electricus (eel) acetylcholine receptor (AChR). This demonstrates the critical role of anti-AChR antibodies in impairing neuromuscular transmission in EAMG. Passive transfer of anti-AChR antibodies from rats with chronic EAMG induced signs of the acute phase of EAMG in normal recipient rats, including invasion of the motor end-plate region by mononuclear inflammatory cells. Clinical, eletrophysiological, histological, and biochemical signs of acute EAMG were observed by 24 h after antibody transfer. Recipient rats developed profound weakness and fatigability, and the posture characteristic of EAMG. Striking weight loss was attributable to dehydration. Recipient rats showed large decreases in amplitude of muscle responses to motor nerve stimulation, and repetitive nerve stimulation induced characteristic decrementing responses. End-plate potentials were not detectable in many muscle fibers, and the amplitudes of miniature end-plate potentials were reduced in the others. Passively transferred EAMG more severely affected the forearm muscles than diaphragm muscles, though neuromuscular transmission was impaired and curare sensitivity was increased in both muscles. Some AChR extracted from the muscles of rats with passively transferred EAMG was found to be complexed with antibody, and the total yield of AChR per rat was decreased. The quantitative decrease in AChR approximately paralleled in time the course of clinical and electrophysiological signs. The amount of AChR increased to normal levels and beyond at the time neuromuscular transmission was improving. The excess of AChR extractable from muscle as the serum antibody level decreased probably represented extrajunctional receptors formed in response to functional denervation caused by phagocytosis of the postsynaptic membrane by macrophages. The amount of antibody required to passively transfer EAMG was less than required to bind all AChR molecules in a rat's musculature. The effectiveness of samll amounts of antibody was probably amplified by the activation of complement and by the destruction of large areas of postsynaptic membrane by phagocytic cells. A self-sustaining autoimmune response to AChR was not provoked in animals with passively transferred EAMG.
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PMID:Pathological mechanisms in experimental autoimmune myasthenia gravis. II. Passive transfer of experimental autoimmune myasthenia gravis in rats with anti-acetylcholine recepotr antibodies. 18 97

A new myasthenic syndrome is described in a patient whose symptoms began soon after birth and included generalized weakness increased by exertion, easy fatigability, hyporeflexia, and refractoriness to anticholinesterase drugs. Electromyography showed a decremental response at all frequencies of stimulation and a repetitive response to single nerve stimulation. Miniature end-plate potentials (mepps) were of normal amplitude but of decreased frequency. The mepp duration and half-decay time were prolonged, and prostigmine was without any addtitional effect. The quantum content of the end-plate potential was decreased due to a reduced store of quanta immediately available for release, but the probability of release was normal. Quantitative electron microscopy demonstrated a 3-fold to 4-fold decrease of nerve terminal size and reduced postsynaptic membrane density. The postsynaptic folds showed focal degeneration, and many were distended by labyrinthine membranous networks that communicated with the synaptic space. Degenerating nuclei were found in the junctional sarcoplasm. The ultrastructural localization of the acetylcholine receptor protein was normal. Acetylcholinesterase (AChE) was absent from the motor end-plates by histochemical and electron cytochemical criteria. Biochemical studies indicated total absence of the end-plate-specific 16 S species of AChE and marked decrease in total muscle AChE. A congenital defect in the molecular assembly of AChE or in its attachment to the postsynaptic membrane might represent the basic abnormality and condition the morphological and physiological alterations.
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PMID:A new myasthenic syndrome with end-plate acetylcholinesterase deficiency, small nerve terminals, and reduced acetylcholine release. 21 17

Antibody against acetylcholine receptor induces an increase in the rate of degradation of acetylcholine receptors on a mouse cell line (BC(3)H-1) and cultured rat skeletal muscle. The increased rate of degradation results in a lowered density of acetylcholine receptors on muscle membrane and a lowered sensitivity to iontophoretically applied acetylcholine. The modulation of acetylcholine receptor is energy, temperature, and time dependent and may be related to antigenic modulation found in other systems. Acetylcholine noise analysis demonstrates that antibody against acetylcholine receptor reduces the channel mean conductance and mean open time slightly. It is concluded that antibody binds to the acetylcholine receptor, impairs its function, and induces receptor degradation. This results in a lowered density of acetylcholine receptor and a lowered sensitivity to acetylcholine. Patients with myasthenia gravis have antibodies to their acetylcholine receptor in their serum. Antigenic modulation of receptor in the muscle of patients with myasthenia gravis could contribute to the observed decrease in amplitudes of miniature endplate potentials and in muscle acetylcholine sensitivity, and the symptoms of muscular weakness.
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PMID:Modulation of acetylcholine receptor by antibody against the receptor. 26 57

The effect of subcutaneous administration of pyridostigmine or neostigmine for 7 to 15 days on neuromuscular transmission has been studied in the rat phrenic nerve-hemidiaphragm preparation. The quantal contents of end-plate potentials at different stimulus rates and the amplitude and frequency of miniature end-plate potentials were compared with those of untreated controls. The rate of release of acetylcholine quanta at high stimulus rates, and the frequency of miniature end-plate potentials, were reduced by pretreatment with both pyridostigmine and neostigmine. Presynaptic effects differed in that the number of quanta released by each nerve impulse at a stimulus rate of 1/sec was not altered by pyridostigmine, but was reduced to 52% of normal by neostigmine. The amplitude of miniature end-plate potentials was reduced to 81% by pretreatment with neostigmine and to 54% by pretreatment with pyridostigmine. The cause appears to be a reduction in the number of acetylcholine receptor sites as a result of disorganisation of the postsynaptic muscle membrane, which may contribute to the muscular weakness associated with the long term use of anticholinesterase agents.
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PMID:Effects of neostigmine and pyridostigmine at the neuromuscular junction. 61 7

An opportunity to investigate the role of anti-acetylcholine receptor antibody (anti-AcH R-antibody) in neonatal myasthenia gravis was presented when an infant was born to a symptomatic myasthenic mother who elected to breast feed the child. Pyridostigmine bromide determinations in plasma and breast milk were made by quantitative gas liquid chromatography. Anti-AcH R-antibody was assayed by an immunoprecipitation method. Simultaneous maternal blood and milk samples did not suggest concentration of pyridostigmine bromide in milk or significant transfer of medication through demand breast feeding. Weakness was not noted in the neonate in spite of high levels of anti-AcH R-antibody demonstrated in her blood. Presence of a markedly elevated anti-AcH R-antibody in a pregnant patient symptomatic with myasthenia gravis does not necessarily predict a clinically affected offspring, nor does the elevated antibody in the infant, presumably acquired transplacentally, necessarily result in clinical symptomatology in the newborn period.
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PMID:The role of anti-acetylcholine receptor antibody in neonatal myasthenia gravis. 75 66

Immunochemical techniques for the study of acetylcholine receptors are described. Immunization of rabbits, rats, guinea pigs, and goats with acetylcholine receptor protein purified from Electrophorus electric organ tissue results in muscular weakness and death due to impaired neuromuscular transmission. Serum from immunized animals contains high concentrations of antibodies directed at receptors from the electric organ and low concentrations of antibodies directed at receptors from skeletal muscle. The detailed similarities between the disease of receptor-immunized animals "experimental autoimmune myasthenia gravis" (EAMG), and myasthenia gravis are compared. Reactions of antisera from animals with EAMG with receptor from Electrophorus and Torpedo are studied. Antireceptor antibodies in these antisera are directed predominantly and determinants other than the acetylcholine-binding site.
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PMID:Immunological studies of acetylcholine receptors. 81 87

A new model of an autoimmune disease of the neuromuscular junction was obtained by injection of acetylcholine receptor purified from rat denervated muscles into Balb/c mice. Anti-rat, then anti-mouse acetylcholine receptor antibodies, appear in mouse serum during the immunization procedure. Electrophysiological investigations performed on immunized mice reveal a neuromuscular block similar to that found in myasthenia gravis. Not a single mouse with objective signs of muscular weakness was lacking anti-mouse acetylcholine receptor antibodies but no correlation was found between their level and the severity of the disease.
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PMID:Experimental myasthenia in Balb/c mice immunized with rat acetylcholine receptor from rat denervated muscle. 106

Rats inoculated once with nicotinic acetylcholine receptor and adjuvants had two episodes of weakness, the first being acute and transient, starting on day 8, and remitting in a few days, the second, chronic, progressive, and appearing after day 20. In the acute phase, the compound action potential and twitch evoked in weak forelimb muscles by maximal nerve stimulus were greatly reduced. Nerve action potentials were normal, however, and the muscle responded to direct electrical stimulation. Using intracellular microelectrodes, miniature end-plate potentials were difficult to find and often were low in amplitude. Many fibers were functionally denervated; no action potential or end-plate potential was evoked by nerve stimulus, although the muscle fiber responded to direct stimulation. In fibers with EEPs the number of acetylcholine quanta released by nerve impulse, the store of quanta readily available for release and the mobilization rate were low. The diaphragm was similarly, but less severely affected. Recovery from the acute phase occurred in a few days with restoration of the response of forelimb muscle to nerve stimulus, even though MEPP amplitude remained low. In the chronic phase, in both forelimb muscle and diaphragm, MEPP were more easily found, but in all rats MEPP amplitude was below normal whether or not there was weakness or a decrement in the EMG. The number of quanta released by nerve stimulus, the store, and the mobilization rate of quanta were normal in all animals. The titer of antibodies ot syngeneic acetylcholine receptor was elevated in all chronic phase animals. The chronic phase is like myasthenia gravis, but rats with MEPP amplitudes as low as those in patients with MG frequently were not weak, because the number of ACh quanta released per nerve impulse is greater in the rat than in man.
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PMID:End-plate potentials in experimental autoimmune myasthenia gravis in rats. 106 90


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