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

Endplate acetylcholinesterase (AChE) consists of globular catalytic subunits attached to the basal lamina by a collagen-like tail. Different genes encode the catalytic subunit and the tail portion of the enzyme. Endplate AChE deficiency was reported previously in a single case (Engel et al., 1977, patient 1). We describe here our observations in four additional patients (patients 2-5). Three cases were sporadic; patients 2 and 3 were sisters. All had generalized weakness increased by exertion but ophthalmoparesis was not a constant feature. All had mild slowing of the pupillary light reflex; other dysautonomic features were absent. None benefited from anticholinesterase therapy. All patients had a decremental electromyogram response; in four of the five patients, single nerve stimuli evoked a repetitive response. Miniature endplate potential amplitude was reduced in patient 5 only. Endplate amplitudes and currents were prolonged but the open-time of the acetylcholine receptor ion channel was normal. In patients 1-4 the quantal content of the endplate potential was reduced due to a reduced number of readily releasable quanta. Quantitative electron microscopy revealed abnormally small nerve terminals, abnormal encasement of the presynaptic membrane by Schwann cells and degeneration of junctional folds and of organelles in the junctional sarcoplasm. Acetylcholinesterase was absent from all endplates of all patients by cytochemical and immunocytochemical criteria. Density gradient ultracentrifugation of muscle extracts from patients 1, 3, 4 and 5 revealed an absence of the collagen-tailed form of the enzyme in patients 1, 3 and 4 but not in patient 5. The kinetic properties of the residual AChE in muscle were normal. Erythrocyte AChE activity and Km values, determined in three patients, were also normal. Studies of the catalytic subunit gene of AChE in patients 2 and 3 revealed no abnormality in those exons that encode the domain to which the tail subunit binds. In patients 1-4 the molecular defect is likely to reside in the gene encoding the tail subunit of AChE, or in a protein necessary to assemble the catalytic and tail subunits. In patient 5, the absence of AChE from the endplate may be due to a faulty tail subunit, a defect in the basal lamina site that binds the tail subunit or failure of transport of the assembled asymmetric enzyme from the cell interior to the basal lamina. The cause of the weakness in these patients is not fully understood but possible mechanisms are discussed.
 ...
PMID:Congenital endplate acetylcholinesterase deficiency. 839 Mar 25

The Congenital Myasthenic Syndromes (CMS) constitute a group of rare genetic disorders affecting neuromuscular transmission. They differ from myasthenia gravis and the Lambert-Eaton myasthenic syndrome, which are autoimmune antibody-mediated conditions. CMS can present at any time from birth to adulthood, though usually within the first 2 yr of life, and result in a spectrum of diseases ranging from mild weakness to severe disability with life-threatening episodes. Several of these syndromes have been well documented, and in recent years fully investigated using a variety of electrophysiological, histochemical, and morphological techniques. In this review we describe the main results of these investigations, and attempt to classify the disorders into groups that can be recognized by the clinician. They include defects in acetylcholine release, absence of the endplate-specific form of acetylcholinesterase, and alterations in the number or function of postsynaptic acetylcholine receptors. Clinical features are described in detail, and treatment reviewed. These disorders involve a potentially large number of candidate genes. Further elucidation of the underlying abnormalities will not only lead to improved treatment, but should contribute to our understanding of the molecular biology of the neuromuscular junction.
 ...
PMID:Congenital myasthenic syndromes. 840 Aug 58

The patient was a 79-year-old male. On CT of the chest, a mass shadow of the anterior mediastinum was found. He did not complain of symptoms, and there were no clinical signs of myasthenia gravis (MG) before surgery. The tumor and the thymus was completely resected. The pathological diagnosis was non-invasive thymoma, and his postoperative course was satisfactory. However, 2 months after the operation, the patient complained of ptosis, diplopia, dysphagia, and muscle weakness, which deteriorated rapidly. The titer of anti-acetylcholine receptor antibody was high at 91.0 nmol/l. By medication of anti-cholinesterase drug and predonin, the symptoms of MG improved. After resection of thymoma, postoperative follow-up with considering the possibility of postoperative MG is necessary.
 ...
PMID:[A case of myasthenia gravis developing after resection of non-invasive thymoma]. 846 68

A middle aged man who inhaled sarin in a train in a subway station in Tokyo in 1995 and showed a variety of symptoms including psychiatric symptoms was reported. He experienced muscle weakness, dyspnea and unconsciousness of sudden onset immediately after exposure to sarin. Marked miosis was observed on admission. Plasma cholinesterase activity was remarkably decreased at that time. He also experienced delirium consisting of visual hallucination, insomnia and irritability at mid-night for more than seven days. These psychiatric symptoms gradually improved without any medication. To date there is no detailed description of such psychiatric symptoms in sarin poisoning.
 ...
PMID:[Psychiatric symptoms following accidental exposure to sarin--a case report]. 852 73

The intermediate syndrome of organophosphate poisoning arises in the time interval between the acute cholinergic crisis of fasciculations and muscle weakness and the delayed neuropathy attributed to inhibition of the neuropathy target esterase. The conclusions derived from salient experimental and clinical studies are that intermediate syndrome relates to the severity of poisoning not the specific organophosphate and to prolonged inhibition of acetylcholinesterase activity of the erythrocytes, brain and muscle endplate with pre and post synaptic impairment of neuromuscular transmission. It is not related to delayed neuropathy.
 ...
PMID:The intermediate syndrome in organophosphate poisoning: an overview of experimental and clinical observations. 852 92

A 52-year-old woman had a 14-year history of stridor attacks. Pulmonary function tests revealed reversible airway obstruction, and bronchial asthma was diagnosed. She also has bilateral ptosis, diplopia, and moderate weakness of all four limbs; a positive edrophonium test confirmed the diagnosis of myasthenia gravis. Although the parasympathetic system plays an important role in the regulation of bronchial tone, in this patient the edrophonium test did not provoke an asthmatic attack or exacerbate pulmonary function, except for increases in sputum production and in frequency of cough. The general weakness was usually worse in the afternoon. The decrease in grip strength and the shortening of arm elevation time also occurred after asthma attacks, which means that general muscle fatigue was caused by the work of breathing. Furthermore, dyspnea increased and pulmonary function worsened when an anti-cholinesterase inhibitor was discontinued, probably because of respiratory muscle weakness. Accordingly, the clinical status of bronchial asthma seemed to change in parallel with that of the myasthenia gravis.
 ...
PMID:[Bronchial asthma complicated by myasthenia gravis]. 869 67

The neuromuscular junction is the site of several myasthenic (mys, muscle; aesthenia, weakness) disorders of autoimmune and genetic origin. The acquired autoimmune conditions are mainly adult-onset and caused by antibodies to specific neuronal and muscle ion channels, but can occur neonatally due to placental transfer of maternal antibodies. This review focuses on the rarer genetic conditions, called congenital myasthenic syndromes (CMS), that often present at birth. Mutations have yet to be characterized for familial infantile myasthenia, acetylcholinesterase deficiency and ACh-receptor deficiency; but genes encoding both structural and functional NMJ protiens should be considered. Other syndromes have recently been shown to involve defects in the functioning of the ACh receptor itself. In particular, eight different mutations have been reported in cases of the slow channel syndrome, a dominant condition associated with point mutations that generate single amino acid changes within the ACh receptor and result in prolonged channel activations. These investigations are providing new insights into the structure and function of the ACh receptor. Further studies of CMS should pave the way for analysis and treatment of disorders involving other synapses in the peripheral and central nervous system.
 ...
PMID:Genes at the junction--candidates for congenital myasthenic syndromes. 900 14

We have compared in two groups of five healthy volunteers, the motor effect of prilocaine i.v. regional anaesthesia of the forearm with and without addition of mivacurium 0.6 mg. Although addition of mivacurium might, theoretically, provide the benefit of increased neuromuscular block with rapid plasma cholinesterase degradation in the isolated limb, we observed prolonged forearm weakness in the mivacurium group using tests of grip strength (median recovery to 90% of control, 80 min (range 60 min to > 8 h) vs control median recovery to 90% of 16 (8-24) min) and bead transfer (median recovery to 90% of control 36 (24-48) min vs control median recovery to 90% of 12 (8-16) min). This weakness was considerably in excess of that predicted by rapid systemic degradation of mivacurium. The mivacurium group experienced symptoms of local anaesthetic toxicity which did not occur in the control group and which could not be replicated by administration of mivacurium alone.
 ...
PMID:Low-dose mivacurium supplementation of prilocaine i.v. regional anaesthesia. 934 38

Two sisters developed slowly progressive limb-girdle weakness in their childhood. The weakness responded to acetylcholinesterase inhibitors. Repetitive nerve stimulation showed decremental responses and single-fiber electromyography demonstrated increased jitter and blocking. Needle electromyography revealed myopathic changes. Antiacetylcholine receptor antibodies were negative. Histologic examinations demonstrated myopathy with tubular aggregates in the muscle fibers while the neuromuscular junctions appeared normal. They were diagnosed with familial limb-girdle myasthenia. This is the first report of this syndrome with morphologic studies of neuromuscular junctions.
 ...
PMID:Familial limb-girdle myasthenia with tubular aggregates. 914 Mar 67

A 34-year-old woman was admitted to our hospital because of ptosis, dysarthria, muscle weakness of upper limbs and skin lesions. At the age of 22 years, she was diagnosed as having systemic lupus erythematosus (SLE) due to the presence of arthritis and high titer of antinuclear antibody. On admission, the high antiacetylcholine receptor antibody titer, along with the positive tensilon test and electromyography established a diagnosis of myasthenia gravis (MG). The demonstration of anti-intercellular antibodies both in cutaneous tissue and blood confirmed the diagnosis of pemphigus. MRI showed hypertrophic thymus. After thymectomy, the myasthenic symptoms aggravated and SLE and pemphigus erythematosus relapsed despite anti-cholinesterase treatment with plasmapheresis. She was then placed on corticosteroid therapy with an improvement of her all symptoms. This very rare case of MG associated with SLE and pemphigus erythematosus suggests that these diseases share common immunological abnormalities.
 ...
PMID:[A case of myasthenia gravis associated with systemic lupus erythematosus and pemphigus erythematosus]. 916 41


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>