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

Clinical Observations. A total of 53 MG patients have been treated with different immunosuppressive methods (alone or combined) with the following effects: Thymectomy was performed in 38 patients. The improvement was excellent in 15, and moderate or uncertain in 20. In three patients severe long-lasting deterioration followed the operation. ACTH treatment (n=32): Initial deterioration during the 5-7 days of heavy ACTH treatment (1000 IU) was followed by an improvement lasting on an average 4 months. The improvement was good or moderate in 78% of the patients. Betamethazone treatment has been tried in six patients where ACTH and azathioprine was ineffective. In four of these patients the results were excellent. Azathioprine treatment has been given to 26 patients for periods up to 7 years. An improvement is measurable after 6-12 weeks and it seems maximal after about 1 year. Of the 26, 80% responded favorable with reduction in the need for cholinesterase inhibitors. Severe complications were seen in three patients with one death. Drainage of thoracic duct lymph was initiated in 14 patients up to 4 weeks with rapid improvement lasting as long as drainage was performed. Long-termed effects of the drainage may be present, however. Retransfusion of homologous cell-free lymph precipitated a return of the myasthenic symptoms. Biochemical Studies on Myasthenic Lymph. Using a membrane preparation from the electric organ from Torpedo marmorata and tritiated Naja naja siamensis neurotoxin we demonstrated a decreasing binding of toxin to the receptor in the presence of MG lymph gamma-globulin fraction. Gammaglobulins from controls showed almost no inhibition of the neurotoxin binding. Immunological Studies. An increased frequency of HL-A1 and 8 was found in female patients. LD typing was also performed. During a period of three weeks of thoracic duct drainage 130X10(9) or about 10% of total number of lymphocytes in the body were removed. In the lymph an initial decrease in the proportion of thymus-derived lymphocytes (T cells) occurred, which was accompanied by a sequent increase in the proportion of bone-marrow-derived lymphocytes (B cells). Towards the end of drainage this effect was reverted. Mitogenic stimulation using lymphocytes from thoracic duct drainage revealed no differences as compared to normal cells. The proportions of T and B cells was studied in the peripheral blood in nine patients treated with ACTH. During treatment there was an initial decrease in the proportion of T cells accompanied by a subsequent rise in the proportion of B cells, which was maximal after 3-10 days. These proportions were reverted to normal 1-5 days after the maximal change. The effect of azathioprine on T and B cells has also been studied.
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PMID:Effects of some immunosuppressive procedures on myasthenia gravis. 18 92

The changes in thymus, spleen and lymph nodes of the mouse after a single cortisone application or a single whole body x-irradiation were investigated morphologically and histochemically. During 24 h the alterations following the cortisone application are at all stages examined indistinguishable from those following the x-irradiation. The first signs of lymphocyte destruction can be observed already in the first two hours after treatment. Almost at the same time macrophages accumulate at the sites of cell death in the lymphatic organs studied. The eosinophils display a different behaviour. While they accompany the macrophages in the thymus already at the first stages, they appear in the spleen and lymph nodes with a latency of 6 and 8 h, respectively. The highest amount of necrotic cells is found ten hours after both treatments. At the same time the accumulation of macrophages and eosinophils reaches its maximum. The cholinesterase in the lymphatic organs is largely the true cholinesterase. The enzyme-activity increases in the cortex of the thymus gradually 6 h after treatment, showing the highest deposit of reaction product at 10 h. In spleen and lymph nodes the cholinesterase shows only slight variations. The possible role of the cholinesterase-activity in these non-cholinergic tissues is discussed.
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PMID:Short time observations of morphological changes and cholinesterase distribution in lymphatic organs of the mouse after corticosteroid and X-ray treatment. 45 46

Menstrually related temporary remissions of myasthenic symptoms are reported to occur in 25 to 50% of female patients. Even though this has been attributed to hormonal changes associated with the menstrual cycle the underlying mechanism of this hormonal influence has remained elusive. The present study demonstrated a cyclical variation in the activity of red cell acetylcholinesterase (EC 3.1.1.7) enzyme (AChE) with a marked reduction at the time of menstrual remission of symptoms of myasthenia. These cyclical changes were abolished by thymectomy. It appears, therefore, that menstrual remission in myasthenia is at least partly due to hormone-induced changes in AChE activity. This process seems to be under the control of the thymus gland.
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PMID:Acetylcholinesterase activity and menstrual remissions in myasthenia gravis. 59 53

(1) Cholinesterase activity was investigated in some human lymphatic organs (palatine tonsil, 'normal' spleen, 'bilharzial' spleen, thymus, lymph node and appendix) using GOMORI'S modification of KOELLE and FRIEDENWALD'S thiocholine iodide method, hydrolyzing acetylthiocholine iodide and butyrylthiocholine iodide. (a) Acetyl- and butyrylcholinesterases seemed to be different enzymes; but when they have the same pattern of activity, the latter generally offers a weaker reaction. (b) All the lymphatic follicles of the tonsil, those found in the cortex of the cervical lymph nodes as well as those present in the appendix, were stainable with both acetyl- and butyrylcholinesterase. (c) Acetylcholinesterase activity was not demonstrated in the Malpighian bodies of the 'normal' spleen, but the reaction was strongly present in the blood vessels (including the central arterioles) as well as in the capsule and the different components of the trabecular system. (d) In 'bilharzial' splenomegaly a relatively strong activity started to appear in the Malpighian corpuscles, manifested as a brownish precipitate in their centres. Also some patchy positive areas began to make their appearance in the tissue of the red pulp and had a particular arrangement around the Malpighian corpuscules, in such a way as to 'wall them off' from the tissue of the red pulp. (e) In the thymus no acetylcholinesterase activity was encountered, except in Hassal's corpuscles and in the trabeculae between the thymic lobules. (2) The data obtained in this work were discussed in relation to previous works in other laboratories and it seems that a species difference exists. (3) Cholinesterases may be present in the lymphatic tissue in order to get rid of some potentially toxic esters resulting from the necrobiotic phenomena accompanying the high mitotic activity found especially in the germinal centres of the lymphoid follicles. (4) There are many unanswered questions about the coexistence of the phosphatases and cholinesterases in the same places; their concomitant association in the lymphatic tissue may represent a special case within the framework of a more general mechanism.
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PMID:Cholinesterase activity in some human lymphatic organs. 95 94

Based on 60 of our own cases and on the medical literature the authors discuss the diagnostic, pathophysiological and therapeutic aspects of myasthenia gravis. Myasthenia is suspected in cases of motor weakness of changing intensity, diminishing by rest. The weak muscles are innervated by different peripheral nerves. At the beginning a weakness of upperlid-muscles, external eye muscles and bulbar muscles is particularly frequent. There is no sensory loss or other neurological symptoms. A transitory disappearance of motor weakness after an intravenous dose of Edrophonium (Tensilon) is a typical diagnostic sign. The effect is less evident with eye-muscle weakness. A typical appearance of potentials after repetitive stimulation of peripheral nerves as well as other characteristics in electrophysiological testing of muscles are of high diagnostic value. This allows differentiation from other types of muscle weakness. In the pathogenesis of myasthenia an autoimmune process related to a persistent thymus gland plays an important part. This leads to an ultrastructural change in the postsynaptic membrane of the muscle fibre. The postsynaptic membrane no longer reacts in a normal way to acetylcholine as a transmitter substance at the level of the motor endplate. Therefore the first step in the treatment of myasthenia consists of cholinesterase-inhibitors, specially Neostigmin (Prostigmin) and Pyridostigmin (Mestinon). Thymectomy is advised in all cases of myasthenia with the exception of the pure ocular form and of myasthenia in patients older than 60 years. The thymus gland is practically always persistent or hypertrophic in myasthenia. The suprasternal access is recommended. A thymoma should always be operated upon because of the danger of malignancy. In cases where thymectomy is not performed or not successful and if cholinesterase-inhibitors are not sufficiently efficient, treatment with corticosteroids or ACTH is recommended.
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PMID:[Pseudoparalytic myasthenia gravis. Diagnostic and therapeutic aspects in 60 separate cases]. 98 76

The present series of thirty patients has led us to certain conclusions concerning the management and treatment of patients with myasthenia gravis. The use of cholinesterase inhibitors alone is reserved for those patients with purely ocular myasthenia whose deficits can be satisfactorily corrected with those agents. Some of those with ocular involvement may be disabled; and in light of our excellent results with that small group, as well as similar findings presented by Fischer et al., patients with disabling or refractory ocular myasthenia should be considered for treatment with prednisone. All other patients with myasthenia are given a course of oral corticosteroids (prednisone) initially at high doses, with subsequent tapering to maintenance, alternate-day low-dose therapy. Cholinesterase inhibitors are used as needed while the patient is receiving corticosteroids. We now anticipate that patients will exhibit sustained improvement within the first two weeks, reaching maximal improvement at about three months. Exacerbations of myasthenic weakness may occur in the early phases of treatment. Such exacerbations have been commonly mild and occur with a mean onset at 5 days, and have a mean duration of 6 days. Most patients have been able to tolerate an alternate-day schedule of prednisone therapy when maintenance levels were achieved. The effective maintenance dose has been determined as the smallest dose of prednisone which allows the patient to maintain maximal improvement. Following the establishment of maximal improvement, patients have been considered for thymectomy. In our experience, the sternum-splitting procedure has been tolerated extremely well by patients exhibiting marked imporvement or remission while on corticosteroids. In those patients where thymectomy is contraindicated, irradiation of the thymus might be considered. Patients are continued on maintenance steroid therapy following surgery for a period of time that has been arbitrary. Currently, we consider an attempt to discontinue steroids at approximately one year reasonable. Should the patient relapse after discontinuation of the medication, oral corticosteroid treatment is reinitiated. Consideration is given to the possibility of recurrent thymus in patients who repeatedly fail to maintain a remission when steroids have been stopped. Our experience has not permitted us to draw firm conclusions concerning how long a time high-dose daily steroid treatment should be continued in patients who show no favorable response to that therapy. Other modes of treatment, such as courses of parenteral ACTH, methyl prednisolone, dexamethazone, or antimetabolites might be considered if there is no response after 12 weeks of high-dose, daily corticosteroid therapy.
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PMID:Long-term prednisone followed by thymectomy in myasthenia gravis. 106 98

Mouse bone marrow and spleen cells formed pure or mixed colonies of up to 80 megakaryocytes in agar cultures after stimulation by medium conditioned by activated mouse lymphoid cells. Megakaryocytes were identified on the basis of their morphology, polyploid mitoses and DNA content, and high cytoplasmic content of acetylcholinesterase. Megakaryocyte colony-forming cells were relatively small with a peak sedimentation velocity of 4.2 mm/hr. Spleen, lymph node, and thymus cells produced the factor stimulating megakaryocyte proliferation after culture in medium containing 2-mercaptoethanol, with or without added mitogens or allogeneic spleen cells. Peak activity in conditioning medium was associated with the small lymphocyte fractions in mouse spleen.
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PMID:Growth of mouse megakaryocyte colonies in vitro. 109 43

A 13-week oral repeated dose toxicity study of Suplatast tosilate (IPD-1151T), a new anti-allergic agent, as well as a 5-week recovery study were carried out at dose levels of 0 (control), 200, 600, 1800 and 5400 mg/kg/day using male and female rats. The results were as follows: 1. In general conditions, salivation were observed in some rats of both sexes given 1800 mg/kg/day. Both sexes given 5400 mg/kg/day disclosed salivation and soft stool and then died after showing ataxic gait, hyperesthesia and convulsion of legs. 2. Inhibition of body weight gain in both sexes given 5400 mg/kg/day were observed from the early stage of the treatment period. 3. The food consumption was decreased from about 3-week and the water consumption was increased from the initiation of study to about 3-week in both sexes given 5400 mg/kg/day. However, both of them were remarkably decreased prior to death. 4. Fecal examination for occult blood showed an increasing tendency in the incidence of positive findings in both sexes given 1800 mg/kg/day. 5. Hematological examination showed slight decreases in erythrocytic parameters in both sexes given 1800 mg/kg/day. In both sexes given 5400 mg/kg/day hemoconcentration was observed, some animals showing decreases in leucocyte and lymphocyte counts and lymphocyte percentage. 6. Biochemical examination showed increases in total and free cholesterol levels in males given 600 mg/kg/day or more, an increased cholinesterase and decreased levels of triglyceride and cholesterol ester ratio in males given 1800 mg/kg/day. An increase in LDH was observed in both sexes given 5400 mg/kg/day and half of these animals also showed increases in GOT and Urea N. 7. The absolute weights of the pituitary, brain, thymus, heart, lungs and kidneys were increased. However, no histopathological lesion was observed in these organs. As treatment-related histological changes, atrophy in the thymus and spleen, dilation in digestive tracts, neuronal necrosis and necrotic foci in the central nervous system, necrosis of lymphocytes in the lymphoid organs and a decrease in bone marrow cell were observed in both sexes given 5400 mg/kg/day. 8. After a 5-week recovery period, above-mentioned changes had disappeared. 9. From the above results, the non-effective dose level was estimated to be 200 mg/kg/day in males and 600 mg/kg/day in females, and toxic dose level 1800-5400 mg/kg/day in both sexes.
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PMID:[A thirteen-week oral repeated dose toxicity study of suplatast tosilate (IPD-1151T) in rats]. 132 Dec 57

In the present study we analyzed development of the rat thymus parasympathetic innervation using histochemical determination of distribution and density of acetylcholinesterase (AChE) positive nerve profiles, as well as biochemical measuring of the activity of this enzyme. Rat thymuses from late embryonal to adult periods of life were analyzed. The AChE-positive nerve profiles were found, for the first time, on day 18 of fetal life in capsule and interlobulary septae, but also in the subcapsulary and cortico-medullary areas. The density of these profiles increased during the thymic development. The AChE positive nerve profiles in subcapsulary region were observed mainly in close proximity to the thymic epithelial cells, while in the cortico-medullary region they were found in apposition to the thymocytes. The biochemical analysis showed that the specific AChE activity in rat thymus was high on day 19 of gestation. A significant increase in the activity of this enzyme was measured by the third day of postnatal development, and its activity remained approximately at the same level up to the day 90. The present results suggest that thymus receives parasympathetic innervation relatively early in ontogeny; in addition, these nerve fibers could be involved in the regulation of the organ activity, at least, through action upon the thymocytes and/or by modulation of the thymic epithelial cell activity.
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PMID:Parasympathetic innervation of the rat thymus during first life period: histochemical and biochemical study. 137 39

Murine thymus has been demonstrated to contain both cholinergic receptors and acetylcholinesterase activity. In the present study we have investigated the presence of the enzyme choline acetyltransferase in this organ, which is responsible for the synthesis of acetylcholine. Results reported here demonstrate that (1) an appreciable amount of the enzyme is already present in the thymus on the day of birth; (2) its expression is developmentally regulated; and (3) thymic atrophy, induced in young (2-week-old) and adult (6-week-old) mice by i.p. injection of hydrocortisone for 2 days, is accompanied by significant reduction of choline acetyltransferase activity only in young mice. Altogether these results demonstrate the presence in the murine thymus of functionally relevant markers of the cholinergic system that might interface the interactions between the nervous and immune systems.
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PMID:Choline acetyltransferase activity in murine thymus. 157 86


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