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 negative chronotropic effects of acetylcholine were studied in the isolated atria of the hearts of albino rats aged 2, 15, 29 and 47 days and adult. In untreated preparations, i.e. with full cholinesterase activity, the strongest effects were observed in newborn animals; with advancing age the reaction grew weaker. If cholinesterase activity was inhibited with physostigmine, the differences between the various age groups were obliterated. It is thus evident that the actual acetylcholine sensitivity of the sinoatrial node tissue does alter during postnatal life, but that growing cholinesterase activity reduces the amount of acetylcholine diffusing from the medium into the acetylcholine receptor zone. The change which takes place in cholinesterase activity in the myocardial tissue during postnatal life is so great that is must be taken into account when considering the development of cholinergic control of cardiac function.
 ...
PMID:Cholinesterases and postnatal development of the negative chronotropic effects of acetylcholine in albino rats. 645 93

To investigate pathogenic mechanisms in experimental autoimmune myasthenia gravis (EAMG) and myasthenia gravis (MG), we studied the acute and chronic effects in rats of injection of rat monoclonal antibodies ( MCABs ) directed against the acetylcholine receptor (AChR). Animals were severely weak 12 h after a single injection, at which time macrophages were found invading endplate regions of muscle and cholinesterase-stained regions were separted from the underlying muscle fibers. Ultrastructural studies showed findings identical to the acute phase of EAMG: degenerating postsynaptic membranes and invasion and phagocytosis of endplate regions by macrophages. Animals receiving sublethal doses of MCAB recovered clinically by 4-5 days after injection. Recovery was accompanied by a progressive decrease in the number of macrophages associated with endplates and reapposition to the myofibers of the cholinesterase-stained regions. Animals injected once, or repeatedly over several months, remained clinically and electromyographically normal after recovery from the initial episode of weakness, but their endplate ultrastructure was highly simplified with blunted or absent synaptic folds and shallow or absent secondary synaptic clefts. These studies demonstrate that anti-AChR MCABs can induce the changes of both acute and chronic EAMG. There is good correlation between the inflammatory changes and the acute clinical disease but poor correlation between morphological and clinical parameters in the chronic syndrome. The latter observation suggests that severe ultrastructural changes, similar to those seen in chronic EAMG and MG, cannot account, at least in rats, for the clinical and electrophysiologic abnormalities of MG.
 ...
PMID:Induction of the morphologic changes of both acute and chronic experimental myasthenia by monoclonal antibody directed against acetylcholine receptor. 661 Feb 75

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.
 ...
PMID:Congenital myasthenia gravis in 13 smooth fox terriers. 684 Dec 51

Embryonic Xenopus muscle cells grown in culture develop discrete patches of high acetylcholine receptor (AChR) density. By following identified muscle cells after staining with fluorescent alpha-bungarotoxin, we have found that many of these AChR patches survive in a fixed position for several days. For AChR patches on the lower surface of the cell (the surface apposed to the culture dish), more than 60% of those which were followed beginning on day 2 survived for a further 4 days. The survival rate was greater when patches were followed from day 3 or later and was almost as high for AChR patches on the upper surface. New AChR patches also formed on all of the muscle cells. When muscle cells were cultured together with spinal cord cells, nerve-muscle contacts developed with a characteristic localization of AChRs along the path of contact. AChR patches did not form elsewhere on these contacted cells. Nerve-contacted muscle cells examined 2 to 3 days after adding spinal cord cells to established (2- to 5-day-old) muscle cultures also exhibited a marked reduction of AChR patches away from the site of contact. This reduction was not due to the nerve having contacted pre-existing AChR patches. Rather, the findings indicate that contact by an appropriate nerve inhibits the formation of AChR patches elsewhere on the contracted muscle cells and reduces the survival of pre-existing AChR patches. Nerve contact also inhibited the formation of cholinesterase (ChE) patches remote from the site of contact and appeared to cause some reduction in the survival of pre-existing ChE patches. Spontaneous twitching was not observed in these experiments, thereby indicating that the remote effects of nerve contact were not mediated by muscle action potentials or contraction. Such remote influences of the nerve may play a role in determining the pattern of innervation on individual muscle cells.
 ...
PMID:Influence of nerve on the formation and survival of acetylcholine receptor and cholinesterase patches on embryonic Xenopus muscle cells in culture. 707 70

The developmental changes in the distribution of acetylcholine receptors (AChRs) and cholinesterase (ChE) were investigated in the posterior latissimus dorsi (PLD) muscle of chick embryos by double staining with rhodamine-labeled erabutoxin b (TMR-Eb) for AChRs and Karnovsky's method for ChE. During the development, the TMR-Eb and ChE positive areas changed in their shapes and sizes. In early stages, the TMR-Eb positive areas appeared as fine fluorescent dots of about 0.3 micrometer in diameter or small aggregates of such dots. These areas then became enlarged and exhibited the following sequential changes in their configuration: spindle-, round-, ring-, C- and finally tree-shaped. The transformation in the configuration of the areas appeared to be caused by the changes of the fluorescent dots in their number and distribution. Simultaneous staining with ChE revealed that at early stages the TMR-Eb positive areas were not stained with ChE, but then they were stained later. The ChE deposits usually accumulated at the borders of the TMR-Eb positive areas and thereby outlined them. Electron microscopy using horseradish peroxidase-labeled erabutoxin b revealed that the fluorescent dots represent the discrete regions of high AChR concentration at the muscle membrane.
 ...
PMID:Acetylcholine receptors and cholinesterase in developing chick skeletal muscle fibers. 713 47

The nature of the defect in congenital myasthenia was investigated in biopsy specimens of intercostal muscle from 5 male patients whose symptoms presented between birth and 2 years of age. Miniature end-plate potentials were reduced in amplitude in all 5 patients. The number of acetylcholine receptors as determined by alpha-bungarotoxin binding was normal in case 1 and reduced in cases, 2, 4, and 5. The shape of the end-plates as shown by autoradiography and cholinesterase staining was normal in case 1 and elongated in cases 2, 4, and 5. In cases 3, alpha-bungarotoxin binding was slowly reversible, and there were some muscle fibers with multiple end-plate regions. The acetylcholine content of the muscle was normal in all 5 cases. None of the patients had serum antibody to human acetylcholine receptor as measured by immunoprecipitation or inhibition of alpha-bungarotoxin binding. We conclude that congenital myasthenia is a heterogeneous condition of nonimmune etiology in which both presynaptic and postsynaptic defects can be found.
 ...
PMID:Congenital myasthenia: end-plate acetylcholine receptors and electrophysiology in five cases. 725 33

The influence of castration upon rat seminal vesicle responses to acetylcholine, carbachol and betanechol has been investigated through the determination of the parameters pD2 (the apparent affinity constant), alpha (the intrinsic activity) and rho (the relative responsiveness) of such drugs on vesicles excised from normal and castrated rats. The pD2 and alpha values for carbachol and betanechol and the pD2 value for acetylcholine increased after orchiectomy; the pD2 increase was greater for the first two drugs than for acetylcholine. No significant difference in the values of rho of the acetylcholine receptor system was obtained after castration. Since carbachol and betanechol are not metabolized by cholinesterase, these results may indicate that the reported change in cholinesterase activity following castration is not the only factor to be considered as responsible for the variation in the seminal vesicle pharmacological reactivity. These results suggest that additional experimentation may be necessary to clarify the mode of action of these drugs in this system.
 ...
PMID:Influence of castration upon the seminal vesicle response to parasympathomimetic drugs. 727 85

Myotomal muscle cells, derived from Xenopus embryos and grown in culture without nerve, develop discrete sites of cholinesterase (ChE) activity on their surface. The spatial relationship of these ChE patches to surface patches of acetylcholine receptors (AChRs) has been examined in the present study by a combination of ChE histochemistry and fluorescent staining of the receptors. ChE patches and AChR patches developed as early as the 1st day in culture and exhibited a high incidence of spatial overlap. The frequency of overlap varied with the age of the culture and ranged from 50 to 98% for patches on the lower cell surface (facing the floor of the culture dish) and from 28 to 79% for patches on the upper cell surface. The high incidence of overlap cannot be explained on the basis of a random distribution of patches since both types of patch occupied less than 3% of the cell surface. ChE and AChR patches also developed when cultures were grown in a serum-free medium as well as when cultures were prepared from young embryos in which muscle innervation had not yet begun. At some patches, the surface membrane was invaginated and at these invaginations, there was also a high incidence of overlap between the ChE and AChR stains. It is concluded that the mechanisms involved in the localization of AChRs and ChE on the surface of Xenopus myotomal muscle cells tend to be closely linked and operate even in the absence of innervation, previous contact by nerve, or electrical and contractile activity. Considered together with previous ultrastructural observations, the present findings suggest that these cells develop elaborate postsynaptic-like specializations even in the absence of neural factors.
 ...
PMID:Localization of cholinesterase at sites of high acetylcholine receptor density on embryonic amphibian muscle cells cultured without nerve. 734 70

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.
 ...
PMID:Arthrogryposis multiplex congenita due to congenital myasthenic syndrome. 761 91

Myasthenia gravis (MG) is an autoimmune disease of neuromuscular transmission associated with the presence of anti-acetylcholine receptor antibodies (anti-AChR Ab). Current treatment of MG includes anti-cholinesterase drugs, thymectomy, corticosteroids, immunosuppressants and plasma exchange (PE). The use of intravenous immune globulin (IVIG) in MG was proposed 10 years ago. Published results of IVIG treatment are discussed and the need for a controlled study is emphasized.
 ...
PMID:Intravenous immune globulin in myasthenia gravis. 803 35


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