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)

Myasthenia gravis is a chronic disease characterized by a fluctuating weakness of voluntary muscles, with a preference for the muscles innervated by the cranial nerves. Ocular symptoms (ptosis, diplopia) were present at onset in 65% of 432 own patients and in 10% of these patients the disease remained confined to the extrinsic eye muscles. A complete remission occurred in 30% of the purely ocular cases within 10 years of onset. The diagnosis depends upon the pattern of weakness, the spontaneous or provoked fluctuation of the symptoms and the favourable response to anticholinesterases. The presence of antibodies against acetylcholine receptor protein is the most recent tool to confirm the diagnosis, but they are absent in 10-20% of the patients with generalized MG and in 20-50% of the purely ocular cases. As the reaction to anticholinesterases in ocular MG is sometimes equivocal or even absent auxillary investigations (electromyography, tonography, nystagmography, curaretest) may be necessary. Oral anticholinesterases (Pyridostigmin, Prostigmin, Ambenomium) usually have a moderate effect on the ptosis and a poor effect on the diplopia so that other measures (ptosishooks, covering one eye) are necessary. In selected patients alternate-day Prednisone is the therapy of choice.
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PMID:The ocular signs and symptoms of myasthenia gravis. 706 4

Acetylcholine receptors were purified to homogeneity from chicken embryonic, adult innervated and denervated muscles, by bio-specific chromatographies using immobilised alpha-neurotoxin and lentil lectin. A minimum specific activity for the pure receptor was estimated to be 6000 nmol alpha-toxin binding sites/g protein. For analysis, the receptors were radio-iodinated or tritiated to high specific radioactivity with succinimidyl-[2,3-3H]propionate. All of the iodinated protein present in the purified receptor preparation reacted with antibody against the pure acetylcholine receptor from Torpedo marmorata electric organ. In the case of all three muscle types used the same oligomeric forms were obtained. The principal form has a sedimentation coefficient of about 9 S, while a minor species (approximately 5S) was also appreciable in crude preparations of embryonic and denervated muscles. Immunization of rabbits with the homogenous receptor from chicken denervated muscle produced muscle weakness characteristic of experimental autoimmune myasthenia gravis. These antisera were equally reactive towards the receptor --125I-alpha-bungarotoxin complexes from chick innervated and denervated muscles. Likewise, the electrophoretic mobilities of the receptors (9-S form) from all three muscle types were identical, as were the isoelectric points of their complexes with 125I-alpha-bungarotoxin. Collectively, these findings and associated ones on subunit structure denote that the 9-S receptor molecules from junctional and extra-junctional area and embryonic stage of chicken muscle are indistinguishable by all criteria yet applied to them.
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PMID:Similarity of acetylcholine receptors of denervated, innervated and embryonic chicken muscles. 1. Molecular species and their purification. 714 Jul 38

A plasma exchange by using the continuous-flow centrifuge blood cell separator (IBM 2997) was carried out in 13 patients with various diseases including myasthenia gravis. The effects of the plasma exchange on blood components and side effects during the procedure were evaluated. In addition, 5 cases with severe myasthenia gravis who had failed to respond to medication were treated by plasma exchange, and the results were as follows: 1. Red blood cells, hemoglobin and hematocrit levels were significantly decreased while white blood cells inclined to increase after plasma exchange. In serum electrolytes and proteins there were no changes. 2. The side effects such as itching and eruption were observed in 46% of the patients. However, they disappeared within a short period. 3. In 2 cases with myasthenia gravis, a significant improvement in muscle weakness was observed by plasma exchange. In these cases, serum levels of the acetylcholine receptor antibody and the circulating immune complex were decreased, as compared with the previous levels. These parameters showed no correlation with severity of the disease.
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PMID:[Fundamental studies with respect to plasma exchange by using continuous-flow centrifuge system and the clinical trial in patients with myasthenia gravis]. 718 99

Mice from eight inbred strains were immunized with acetylcholine receptor (AChR) purified from Torpedo californica. All mice developed high concentrations of serum antibodies (10(-6) M) against the immunogen and approximately 80% possessed antibodies reactive with mouse nicotinic AChR. 33% of the mice immunized (n = 236) developed muscular weakness and flaccid paralysis. Behavioral, electrophysiological, and pharmacological similarities were found between the experimentally induced muscular weakness and the disease myasthenia gravis. Susceptibility to experimental myasthenia was found to be strain dependent in that the frequency of paralysis was much greater in some strains than others. The occurrence of muscular weakness and flaccid paralysis did not correlate with the concentration of antibodies reactive with T. californica or mouse AChR. Anti-receptor antibodies which increased the rate of AChR degradation on the mouse muscle cell line, BC3H-1, were found in the serum of both myasthenic and nonmyasthenic mice. 40% of the mice tested possessed antibodies reactive with antigenic determinants present on mouse receptor but not T. californica receptor. The occurrence of antibodies unique to mouse receptor did not correlate with myasthenia. Thus, myasthenia in the mouse does not occur simply as a consequence of the presence of antibodies directed against cell surface antigenic determinants of AChR. If anti-AChR antibodies are both necessary and sufficient for the induction of myasthenia, then these studies suggest that populations of a particular structure and/or specificity are required. It is anticipated that the mouse model of myasthenia gravis will permit the regulation of the anti-receptor immune response to be studied in detail.
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PMID:Experimental myasthenia gravis. A murine system. 735 Feb 47

Myasthenia Gravis (MG) is an autoimmune disorder which compromises neuromuscular transmission. The hallmark of the disorder is fatigue with repetitive activity. Patients may experience symptoms ranging from double vision, ptosis and weak voice to choking, shortness of breath, generalized weakness and respiratory failure. The clinical diagnosis is confirmed by identification of a decremental response to repetitive nerve stimulation by electromyography (EMG), the presence of serum antibodies to the muscle acetylcholine receptor (AChR), or an improvement in strength with administration of intravenous edrophonium. With improvements in critical care and immunosuppressive treatments, MG is rarely the grave disease it once was, but because of the odd fatiguing symptoms and relative rarity of the disorder, patients are frequently misdiagnosed and their special needs overlooked. The nature of MG, with its acute and chronic components, creates complex needs for affected individuals and their families. The advanced practice nurse in collaboration with a neurologist in the outpatient setting is positioned to address these needs in an ongoing case management role.
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PMID:Myasthenia gravis: pathophysiology, diagnosis and collaborative care. 749 22

Autoantibodies directed against the acetylcholine receptor (AChR) lead to AChR loss and muscular weakness in myasthenia gravis and its experimental model, experimental autoimmune myasthenia gravis (EAMG). The role of different anti-AChR sequences and specificities in the pathogenesis of EAMG was investigated by sequencing a panel of 19 mouse mAbs, previously elicited against Torpedo and human AChR, that bound to at least four different epitope regions. The pathogenicity of eight mAbs that cross-reacted with mouse or rat AChR was tested. EAMG was induced by four mAbs against the main immunogenic region (MIR). Sequence analysis of different anti-AChR specificities showed a large diversity of H and L chain sequences. Highly homologous H chain sequences (> 90%) were found among some mAbs with similar specificities, whereas highly homologous L chain sequences were not restricted to Abs of a particular fine specificity. Sharing of a highly homologous VH gene or an identical DJH region was observed among three of four pathogenic anti-MIR mAbs, obtained by immunization with AChRs from different species. The VH genes of these three pathogenic mAbs were closely related to PC7183 germline genes indicating that some pathogenic Abs may already be present in the germline repertoire.
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PMID:Sequence analysis of anti-AChR antibodies in experimental autoimmune myasthenia gravis. 753 19

We reported a unique case of myasthenia gravis in association with tuberculous mediastinal lymphadenitis. A 56-year-old man suffering from generalized myasthenia gravis underwent thymothymectomy followed by good clinical recovery for 2 years. Thereafter, the patient complained of acute onset of ptosis, diplopia, dysphagia and limb weakness with elevated titers of serum anti-acetylcholine receptor antibody. CT scans of the chest showed a mediastinal lymphadenopathy and the Thallium-201 SPECT revealed an abnormal mediastinal accumulation, suggesting recurrence of thymoma in the mediastinal lymphonode. Histologically, the re-operated mediastinal tumor was of tuberculous lymphadenitis. This patient gives us a caution that we must guard against errors in differentiation between thymoma and tuberculous mediastinal lymphadenitis, particularly when myasthenic patients with mediastinal tumors are expected to receive the corticosteroids therapy. (120 words).
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PMID:[Acute deterioration of myasthenia gravis in association with tuberculous mediastinal lymphadenitis, simulating recurrence of thymoma. A case report]. 761 72

Two children, now 5 1/2 and 6 years of age, presented as neonates with hypotonia, multiple joint contractures, ptosis, extraocular weakness, bulbar symptoms, and respiratory distress. Fluctuations and episodic exacerbations of weakness necessitated respiratory support. Both children are developmentally delayed and cannot walk independently, although one child underwent bilateral tenotomies. Biochemical investigations and electromyography, including slow-rate, repetitive nerve stimulation, were normal. Acetylcholine receptor antibodies in serum were absent. Single-fiber electromyography with axonal stimulation revealed prolonged mean jitter in the tibialis anterior and extensor digitorum muscles, with more than 2 abnormal individual jitter values in each muscle. Muscle biopsy demonstrated normal pattern and morphology of muscle fibers; immunohistochemical staining for cholinesterase was positive. Electron microscopy revealed abnormalities in motor endplates: atrophy, flattening of primary synaptic clefts, and paucity of side branches. These findings represent one of the postsynaptic abnormalities (i.e., acetylcholine receptor deficiency or paucity of synaptic folds). Both children improved clinically on pyridostigmine therapy. Arthrogryposis congenital multiplex due to congenital myasthenic syndrome, as diagnosed in our patients, has been reported once before. The diagnosis can be established by clinical history, neurologic examination, and electrophysiologic and pathologic findings. Clinical improvement can be achieved with high-dose anticholinesterase therapy.
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PMID:Arthrogryposis multiplex congenita due to congenital myasthenic syndrome. 761 91

Myasthenia gravis is an autoimmune disease in which autoantibodies specific to the acetylcholine receptor (AChR) are formed, leading to a gradual destruction of the receptors in muscles that are responsible for picking up nerve impulses, and results in weakness and eventual loss of muscle function. The novel immunomodulating drug leflunomide (HWA 486) has been shown to be very effective in preventing and halting ongoing disease in an array of experimental autoimmune disorders and reactions leading to organ graft rejection. Further, recent data from phase II clinical trials indicate that this drug is efficacious and is safe in humans with rheumatoid arthritis. In the studies reported here, we found that rats immunized with AChR-protein and not receiving leflunomide developed experimental myasthenia gravis (EMG) between day 7 and 11 post-immunization, and about 79% of these animals expressed clinical signs of disease. Treatment of AChR-protein immunized rats with leflunomide, from the day of disease induction, totally suppressed the development of EMG. Thus, the results we have obtained using leflunomide in EMG indicate that this drug could be beneficial in combating myasthenia gravis in humans.
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PMID:Leflunomide prevents the development of experimentally induced myasthenia gravis. 767 79

Myasthenia gravis (MG) is an organ-specific autoimmune disease caused by an antibody-mediated assault on the muscle nicotinic acetylcholine receptor (AChR) at the neuromuscular junction. Binding of antibodies to the AChR leads to loss of functional AChRs and impairs the neuromuscular signal transmission, resulting in muscular weakness. Although a great deal of information on the immunopathological mechanisms involved in AChR destruction exists due to well-characterized animal models, it is not known which etiological factors determine the susceptibility for the disease. This review gives an overview of the literature on the AChR, MG and experimental models for this autoimmune disease.
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PMID:Myasthenia gravis: an autoimmune response against the acetylcholine receptor. 768 5


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