Effect of Blood Serum From Patients With Myasthenia Gravis on the Synthesis of Acetylcholine in Vitro1

Torda, Clara; Wolff, Harold G.

doi:10.1172/jci101535

Cited by 24 publications

(4 citation statements)

References 5 publications

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“…2 Since the completion of this manuscript three additional patients with myasthenia gravis have been given Patient R. G., a 45 year old woman, had had myasthenia gravis for ten years. She received a total of 180 mg. of neostigmine bromide a day, distributed over the waking hours, taken in three hourly intervals, 25 mg. of ephedrine sulfate once a day, and 1 gram of potassium chloride three times a day.…”

Section: Methodsmentioning

confidence: 99%

“…Acetylcholine synthesis in the presence of serum was studied following the method described by Torda and Wolff (2) before the injection period of the hormone, the third day after completion of the injection period, and biweekly thereafter. The method consists of incubation of a tissue containing choline acetylase with blood serum and determination of the amount of acetylcholine formed during the period of incubation.…”

Section: Biochemical Studies (Acetylcholine Synthesis)mentioning

confidence: 99%

“…The adrenocorticotrophic hormone of the pituitary gland has been administered to patients with myasthenia gravis mainly on the basis of the following observations and inferences: (1) the immediate cause of the symptoms of myasthenia gravis is a decrease of acetylcholine synthesis (1)(2)(3)(4); (2) administration of the adrenojorticotrophic hormone increases acetylcholine synthesis' in vivo (5); (3) increase of the lymphatic tissue (round-cell infiltration of various organs, mainly striated muscle [6]) and "hyperfunctioning" thymus (7) have been found in patients with myasthenia gravis. Tissue fractionation studies (8,9) have shown that one of the sources of the substances that inhibit acetylcholine synthesis is the thymus.…”

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confidence: 99%

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Effects of Adrenocorticotrophic Hormone on Neuro-Muscular Function in Patients with Myasthenia Gravis.

Torda

Wolff

1949

Experimental Biology and Medicine

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The adrenocorticotrophic hormone of the pituitary gland has been administered to patients with myasthenia gravis mainly on the basis of the following observations and inferences: (1) the immediate cause of the symptoms of myasthenia gravis is a decrease of acetylcholine synthesis(1-4); (2) administration of the adrenojorticotrophic hormone increases acetylcholine synthesis' in vivo (5); (3) increase of the lymphatic tissue (round-cell infiltration of various organs, mainly striated muscle [6]) and "hyperfunctioning" thymus (7) have been found in patients with myasthenia gravis. Tissue fractionation studies (8,9) have shown that one of the sources of the substances that inhibit acetylcholine synthesis is the thymus. Administration of the adrenocorticotrophic hormone induces reduction in the mass of the thymus and the lymphatic tissue (10, 11); (4) removal of the pituitary gland in rats induces changes in the electromyogram (12) that closely resemble the abnormalities noted in patients with myasthenia gravis (13, 14); (5) the pituitary gland of several patients who died of myasthenia gravis showed accumulation of an eosinophilic colloid material suggesting altered function of the gland (15)(16)(17)(18)(19).This report aims to illuminate the nature of myasthenia gravis by a further analysis of its phenomenology. Therapeutic implications are outside its scope. MATERIALThe effect of the administration of adrenocorticotrophic hormone of the pituitary gland was studied in five patients moderately to severely ill with myasthenia gravis.2 1 Published with permission of the Chief Medical Director, Department of Medicine and Surgery, Veterans Administration, who assumes no responsibility for the opinions expressed or conclusions drawn by the authors.2 Since the completion of this manuscript three additional patients with myasthenia gravis have been given Patient R. G., a 45 year old woman, had had myasthenia gravis for ten years. She received a total of 180 mg. of neostigmine bromide a day, distributed over the waking hours, taken in three hourly intervals, 25 mg. of ephedrine sulfate once a day, and 1 gram of potassium chloride three times a day. While on this medication, she was able to rise from her bed and to sit by it in an armchair. She was barely able to walk very short distances when aided by an attendant. She had ptosis of the left fe-lid; her extraocular movements were limited in all directions. She also exhibited marked weakness and easy fatigability of the muscles of the palate, tongue, deglutition, chewing, face, and extremities. In addition, she had severe anorexia. Patknt H. L., a 24 year old woman, had had myasthenia graves for four years. She received a total of 300 mg. of neostigmine bromide a day, distributed over the waking hours, taken in three hourly intervals, 25 mg. of ephedrine sulfate three times a day, 1 gram of potassium chloride three times a day, and 0.13 gram of guanidine hydrochloride three times a day. When on this medication, she was able to walk but showed severe general weakness, ptosis ...

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Section: Methodsmentioning

confidence: 99%

Section: Biochemical Studies (Acetylcholine Synthesis)mentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of Adrenocorticotrophic Hormone on Neuro-Muscular Function in Patients with Myasthenia Gravis.

Torda

Wolff

1949

Experimental Biology and Medicine

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“…Steroids are first-line drugs for immunomodulatory therapy, but caution is needed because of their possible initial worsening of MG [78,79]. The EFNS guidelines recommend starting steroids at low doses, with a gradual increase or alternate-day doses [57].…”

Section: Preoperative Usementioning

confidence: 99%

Perioperative management in myasthenia gravis: republication of a systematic review and a proposal by the guideline committee of the Japanese Association for Chest Surgery 2014

Kadota

Horio

Mori

et al. 2015

Gen Thorac Cardiovasc Surg

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Thymectomy is regarded as a useful therapeutic option for myasthenia gravis (MG), though perioperative management in MG patients is largely empirical. While evidence-based medicine is limited in the perioperative management of MG patients, treatment guidelines are required as a benchmark. We selected issues faced by physicians in clinical practice in the perioperative management of extended thymectomy for MG, and examined them with a review of the literature. The present guidelines have reached the stage of consensus within the Japanese Association for Chest Surgery.

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Choline Acetyltransferase and Acetylcholinesterase

Gentner¹

1972

Arch Neurol

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Choline acetyltransferase, acetylcholinesterase, and pseudocholinesterase levels were measured in needle biopsy samples of deltoid muscle from subjects with myasthenia gravis and from normal controls. Choline acetyltransferase activities were about 30% lower and acetylcholinesterase activities about 45% lower in myasthenics as compared with controls. These decreased activities, however, are not significant in the cause of the disease; it is postulated that the primary defect at the neuromuscular junction may be the presence of a false transmitter in the synaptic vesicle or defective release of the vesicle contents at the synaptic cleft. (27:521-525, 1972) Jthough myasthenia gravis was first de¬ scribed 300 years ago1 and effective drug therapy has been used since 1934,2 the cause and basic defect are still unknown. It is generally agreed that defective transmission across the neuromuscular junction is direct¬ ly involved.35 The effectiveness of anticholinesterase drugs has focused considerable attention on the enzymes catalyzing synthe¬ sis and hydrolysis of acetylcholine (ACh). Numerous investigators have measured lev¬ els of cholinesterase (ChE) in serum of myasthénies, generally finding no difference from controls.6 There have been few studies of ChE levels in muscle of myasthénies. Jones and Stadie7 reported on one patient and found no difference from controls. Goodman et al8 found that neostigmine bro¬ mide (Prostigmine [France]; Prostigmin Bromide, comparable US product) lowered ChE levels in one myasthénie, but they did not have any normal controls. Wilson et al8reported that ChE levels in myasthénie mus¬ cle averaged 20% lower than controls, but this was not statistically significant due to the large scatter in their data. Rosenberg et al10 in a study of three myasthénies, found no difference from controls in acetylcholin¬ esterase (AChE) activities, but found a significant 26% reduction in choline acetyl¬ transferase (ChAc) specific activities. How¬ ever, that study was not ideal, since the biopsied muscle samples were infused with propoxycaine hydrochloride which inhibited the ChAc activity by 50%. This left open the possibility that myasthénies were merely more sensitive to propoxycaine. Accordingly, we have now extended and refined these studies with larger sample sizes and a new needle biopsy technique which allows us to circumvent the difficulties with propoxycaine. Methods and MaterialsNeedle biopsy samples of human muscle were obtained from the deltoid muscle of volun¬ teers using a Vim disposable biopsy needle. The motor point was located on the skin by stimulation with a constant current stimulator

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Effect of Blood Serum From Patients With Myasthenia Gravis on the Synthesis of Acetylcholine in Vitro1

Cited by 24 publications

References 5 publications

Effects of Adrenocorticotrophic Hormone on Neuro-Muscular Function in Patients with Myasthenia Gravis.

Effects of Adrenocorticotrophic Hormone on Neuro-Muscular Function in Patients with Myasthenia Gravis.

Perioperative management in myasthenia gravis: republication of a systematic review and a proposal by the guideline committee of the Japanese Association for Chest Surgery 2014

Choline Acetyltransferase and Acetylcholinesterase

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