Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Randomised and controlled treatment studies of juvenile-onset myasthenia gravis have not been published. We therefore report our retrospective analysis of 79 patients with juvenile-onset myasthenia gravis observed for as long as 30 years. The mean age at onset was 13.7 years and median follow-up 7.7 years. The initial presentation was generalised disease in 90% and ocular disease in the remaining patients. Sixty-five patients (82%) were thymectomised. In 14 of these, treatment consisted of a combination of azathioprine (2-3 mg/kg), corticosteroids (prednisolone up to 60 mg for a maximum duration of 12 months with subsequent tapering) and acetylcholinesterase (AChE) inhibitors, and of azathioprine and AChE inhibitors in 27 patients. One patient received azathioprine and 22 AChE inhibitors only; in another no further medication was necessary. In the severely affected group (n = 16), plasmapheresis was performed additionally before thymectomy and continued for some time after the operation. Treatment was started between 1 and 14 months (mean 2.4 months) after the onset of myasthenic symptoms. No thymectomy was done in 14 patients, and immunosuppressive treatment and AChE inhibitors were given in 9 of these cases. One patient received azathioprine only; 4 patients received AChE inhibitors only. The histology of the thymus gland showed follicular hyperplasia in 89% of the 65 thymectomised patients and normal findings in the remainder. Remission occurred in 60% of patients who underwent thymectomy and in 29% of those who were not thymectomised. Hyperthyroidism (6 patients, 8%), diabetes mellitus (2 patients, 3%) and rheumatoid arthritis (2 patients, 3%) were the most frequent associated immune-mediated diseases. Epileptic seizures and neoplasia were coincident diseases in 2 (3%) and 3 (4%) patients, respectively. There were no deaths from thymectomy or from immunosupression. This open, retrospective analysis suggests that juvenile-onset myasthenia gravis can be treated satisfactorily in most patients by the use of thymectomy and/or immunosupressive medication.
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PMID:Outcome in juvenile-onset myasthenia gravis: a retrospective study with long-term follow-up of 79 patients. 930 59

Interrelations among changes in 11-oxycorticosteroids (11-OSC) in blood plasma, catecholamines (CA), and acetylcholinesterase (AChE) activity in nerve fibres of the thymus, as well as qualitative content and proliferative capacity of thymic and blood cells under the effect of the rat recombinant interleukin-1 beta (IL-1 beta) normally and under conditions of hypothalamic-pituitary-adrenocortical depression, were studied. The changes were the most obvious within 15 and 120 min following the IL-1 beta administration: elevation of the 11-OSC, increase in the CA content, and decrease in the AChE activity in thymic nerve fibres. Preliminary administration of dexamethasone prevented the effects.
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PMID:[Alternative paths of zinc transepithelial transport in the small intestine]. 980 81

The time course of IL-1beta effects on autonomic nervous activity and the functional state of lymphocytes in the rat thymus (15, 120 min and 24 hours) was studied. At 15 and 120 min after IL-1beta administration, an elevation of corticosterone (CS) in blood plasma, an increase in catecholamine (CA) content and a decrease in acetylcholinesterase (AChE) activity in thymic nerve fibers were observed as compared to intact and vehicle-treated animals. At 120 min, the percentage of T lymphocytes decreased in the thymus and increased nonsignificantly in the blood, as evaluated by flow cytometry. During this period, the proliferative response of thymocytes to mitogen was twice as high in animals treated with IL-1beta or vehicle as compared to intact rats, but did not differ 15 min and 24 hours later. Treatment with dexamethasone (DEX) prior to the administration of IL-1beta prevented the CS increase, diminished the CA increase and enhanced AChE activity in nerve fibers, and led to inhibition of the proliferative response of thymocytes to mitogen. Thus, IL-1beta induces substantial changes in the neuro-humoral supply of the rat thymus. The direction of the immune function changes depends on the balance between the CS content in blood, and CA and AChE activity in the nerve fibers of the rat thymus.
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PMID:Effects of interleukin-1beta on autonomic nervous activity and functional state of immunocompetent cells in the rat thymus. 983 Nov 75

Interrelations among changes in 11-oxycorticosteroids (11-OSC) in blood plasma, catecholamines (CA), and acetylcholinesterase (AChE) activity in nerve fibres of the thymus, as well as qualitative content and proliferative capacity of thymic and blood cells under the effect of the rat recombinant interleukin-1 beta (IL-1beta) normally and under conditions of hypothalamic-pituitary-adrenocortical depression, were studied. The changes were the most obvious within 15 and 120 min following the IL-2 beta administration: elevation of the 11-OSC, increase in the CA content, and decrease in the AChE activity in thymic nerve fibres. Preliminary administration of dexamethasone prevented the effects.
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PMID:[Neuroimmune relations in the rat thymus caused by recombinant interleukin-1beta administration]. 986 30

Acetylcholinesterase (AChE) localization in the human thymus has been studied by biochemical and morphological methods during development and aging. The occurrence, the amount and the distribution of acetylcholinesterase and the changes with age were examined in 24 human thymuses. The whole human thymus was removed during autopsies in males of the following age-groups: prenatal of six months, new-born, infant, young, adult and elderly. The thymuses were weighed, measured and dissected: the microanatomical details were stained with Eosin-orange, nervous structures were identified by means of Bodian's method. Protein content was determined with biochemical methods. Histoenzymatical and biochemical demonstration of acetylcholinesterase was performed. The morphological results obtained were submitted to quantitative image analysis. Our results show that the thymic microenvironment changes with age; moreover, an increase of acetylcholinesterase-positive structures can be observed with age. Biochemical results are in agreement with morphological results and both are confirmed by the outcome of quantitative analysis of images. Acetylcholinesterase activity in human thymus may play a key role in thymic functions.
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PMID:Quantification of acetylcholinesterase-positive structures in human thymus during development and aging. 1056 61

To assess a putative role of the neural pathways in transfer of information from the gonads to the thymus, adult AO rats were orchidectomized (ORX) or sham ORX (controls); sacrificed 1, 3, 7, or 15 days later and their thymi were analyzed for: (a) the concentrations of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) and distribution of monoamine-containing nerve profiles and (b) the acetylcholinesterase (AChE) activity and distribution of AChE-containing nerve profiles. Three days after the castration, an elevation in the level of both catecholamines, reflecting an increase in the overall intensity of nerve fibers autofluorescence, was found. Seven days post castration neither NA nor DA concentration differed from the appropriate control values, while 15 days after the surgery the concentration of NA was lower than that in the controls, most likely, due to diminished density of noradrenergic nerve profiles. In both the rats sacrificed 7 and 15 days after orchidectomy the concentration of 5-HT was reduced as result of a decrease in the density of 5-HT-containing autofluorescent cells. The activity of AChE was depressed one day after the surgery; then increased, so that 3 days post castration its value was higher than that in the sham ORX. After this increase, AChE activity decreased being, at postoperative day 7 and 15, lower than that in the controls. It seems that this decrease in AChE activity reflected, not only a reduction in the density of AChE-containing nerve fibers, but also a decrease in the density of AChE positive cells. Thus, the results indicate that orchidectomy can evoke changes in the T-cell maturation altering modulatory influences on this process coming via neural route, as well as those coming from the mast cells and AChE positive epithelial cells which constitute important component of the thymus microenvironment.
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PMID:Orchidectomy affects the innervation of the rat thymus. 1068 Nov 21

It has been hypothesized that maturational processes within the hypothalamo-pituitary-gonadal (HPG) axis and thymus are reciprocally regulated via neural pathways. To test this hypothesis, in the thymi of adult rats orchidectomized (ORX) at age of 1 (ORX-1), 7 (ORX-7) and 30 days (ORX-30): (i) noradrenaline (NA), dopamine (DA) and serotonin (5-HT) contents and acetylcholinesterase (AChE) activity were measured and (ii) the distribution of monoamine- and AChE-containing nerves and cells was examined by a sucrose phosphate glyoxylic acid (SPG) method and enzyme histochemistry, respectively. In all groups of ORX rats, the thymus weight was significantly increased over that in sham-ORX control rats. In the ORX-1 rats, the increase in the thymus weight was accompanied by a proportional increase in the content of both catecholamines and 5-HT; consequently the concentration of each of them remained unaltered. In these animals, the density of both SPG-stained thymus nerve fibers and cells also remained unchanged. In the ORX-7 rats, the rise in the thymus weight was followed by a proportional increase in the content of all monoamines, except for NA which was reduced. Therefore, in these rats neither the thymus concentrations of DA nor that of 5-HT differed from controls, while the concentration of NA was significantly decreased. The reduction in both NA content and concentration reflected a diminished density of SPG-positive nerve profiles. In the ORX-30 rats, the increase in thymus weight was neither paralleled by a proportional increase in the DA content nor in 5-HT, while the content of NA was decreased. Thus, in their thymi the concentration of both NA and DA, as well as that of 5-HT, were significantly reduced. In parallel with these changes, a decreased density of thymic SPG-positive nerve fibers and cells was found. In all ORX rats, the pattern of intrathymic distribution of SPG-positive fibers and cells remained unchanged. Orchidectomy affected neither the activity of AChE (expressed per gram of tissue) nor the density of AChE-positive nerves and cells in the thymus. As the changes in the density of adrenergic nerve fibers in the thymus from ORX rats were not followed by similar alterations in the density of AChE-containing nerve fibers, it does not seem likely that NA and AChE are colocalized in the thymus nerve fibers. The results also suggest that there is a critical period during ontogenesis when changes within the HPG axis evoked by orchidectomy can affect the sympathetic nerve input to the rat thymus and therefore, most likely, development and function of the organ.
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PMID:Castration of sexually immature rats affects sympathetic innervation of the adult thymus. 1068 14

Acetylcholine (ACh) is well known as a neurotransmitter in both the central and peripheral nervous systems in mammalian species. Both muscarinic and nicotinic ACh receptors have been identified in lymphocytes isolated from thymus, lymph node, spleen, and peripheral blood, and their stimulation by muscarinic and nicotinic agonists elicits a variety of functional and biochemical effects. On the basis of these findings, it has been postulated that the parasympathetic nervous system may play a role in immune-neurohumoral crosstalk. However, ACh present in the blood of several species has been localized to lymphocytes from various origins using radioimmunoassay. Moreover, using Northern blots or reverse transcription-polymerase chain reaction, expression of choline acetyltransferase, an ACh synthesizing enzyme, has been identified in human blood mononuclear leukocytes, human leukemic T-cell lines, and rat lymphocytes. Stimulation of T-lymphocytes with phytohemagglutinin activates the lymphoid cholinergic system, as evidenced by increased synthesis and release of ACh, increased acetylcholinesterase activity, and the increased expression of mRNA encoding choline acetyltransferase and ACh receptors. The observation that muscarinic receptor stimulation by ACh or agonists increases in [Ca(2)+](i) and up-regulates c-fos expression strongly argues that ACh synthesized and released from T-lymphocytes acts as an autocrine and/or paracrine factor regulating immune function. In summary, these data present a compelling picture in which immune function is not only regulated by the cytokine system, but is also under the control of an independent, lymphoid cholinergic system.
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PMID:Extraneuronal cholinergic system in lymphocytes. 1076 May 45

Experiments on Wistar rats showed that acute poisoning with organophosphorus compound dimethyl dichlorovinyl phosphate (0.5 LD(50)) was accompanied by two opposite effects: inhibition of acetylcholinesterase in T lymphocytes leading to suppression of thymus-dependent antibody formation (predominant effect) and acetylcholine-induced stimulation of antibody production. Acetylcholine activated acetylcholinesterase in intact T cells.
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PMID:Role of anticholinesterase mechanism in suppression of antibody formation during acute poisoning with organophosphorus compounds. 1155 55

The term seronegative myasthenia gravis (SNMG) refers to the generalized disease without detectable anti-acetylcholine receptor (anti-AChR) antibodies. In these patients, IgG antibodies against the muscle-specific kinase (MuSK) have been described, which reduced agrin-induced AChR clustering in vitro. We have assayed anti-MuSK antibodies in 78 patients with SNMG, who have been followed for many years in our Institution. Here we describe the clinical phenotype of the 37 patients whose results were positive on this assay. MG with anti-MuSK antibodies was characterized by a striking prevalence of female patients (eight men and 29 women). Age of onset ranged from 6 to 68 years, with 56.8% of patients presenting under 40 years of age. All these patients shared a similar pattern of muscle weakness, with prevalent involvement of cranial and bulbar muscles and a high frequency of respiratory crises; the involvement of limb muscles was comparatively less severe and inconsistent. Single-fibre-EMG confirmed the most sensitive examination in the EMG diagnosis of MuSK-positive disease, while, owing to weakness topography, repetitive nerve stimulation in limb muscles was diagnostic in 56.8% of cases. The effect of edrophonium (or neostigmine) injection was equivocal or negative in 11 of 37 patients (29.7%), and the response to oral pyridostigmine was even more unsatisfactory, ranging from mild benefit to overt intolerance. In thymectomized patients, thymus was normal for age or atrophied, and no benefit from surgery was noticed. Thirty-five of 37 patients were given immunosuppressive therapy and 22 received plasma-exchange. The course of the disease was often characterized by periodic exacerbation phases requiring hospitalization and even assisted ventilation; plasma-exchange produced marked improvement in these cases. At the end of the observation period, most patients, although improved, were still symptomatic, having developed permanent facial and pharyngeal weakness together with some atrophy of facial muscles. MuSK-negative disease was comparatively more heterogeneous. Most patients were affected with mild to moderate symptoms and responded well to pharmacological treatment; however, a few subjects in this group had severe refractory disease, poorly responsive to both acetylcholinesterase inhibitors and immunosuppressants.
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PMID:Clinical correlates with anti-MuSK antibodies in generalized seronegative myasthenia gravis. 1282 9


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