The History of Myasthenia Gravis

Since Willis described 'fatigable weakness' in 1672, most physicians consider it as a kind of hysteria due to the inconsistent fluctuation of symptoms. Erb presented three cases of 'bulbal palsy' in the 1870s, and Oppenheim and Hopper considered myasthenia gravis as a disease similar to curare poisoning and as a disease induced by attack of the motor centers by intrinsic toxins, respectively. In 1903, Elliot suggested that a 'chemical substance' mediates the nerve impulses at synapse. However, it was not until 1921 that this was demonstrated by Loewi, who provided evidence from the famous two-frog-hearts experiment. Dale later revealed the substance to be acetylcholine, and he also suggested that myasthenia gravis is due to a problem with the motor end plate. In 1934, Walker was prompted by the resemblance between myasthenia gravis and curare poisoning to apply physostigmine, a curare-poisoning antidote, to a patient, which produced a dramatic result. Since then the use of anticholinesterase inhibitors has been adopted for standard therapeutic modality. Some prominent surgeons have also applied thymectomy as a surgical modality. The most recent focus of myasthenia gravis has been immunological. In 1960, Simpson proposed the autoimmune hypothesis, and Chang et al. showed that snake venom contained a selective antagonist of the nicotinic acetylcholine receptor, alpha-bungarotoxin. The immunization of rabbits with acetylcholine receptor purified from the electrical organs of electric eels by Patrick et al. induced myasthenic symptoms and signs, and these were reversed by acetylcholinesterase inhibitors. The role of the autoimmune system has led to the introduction of an immunosuppressive modality and plasma exchange to the field of clinical neurology.

Cytogenetic characterization of the strongly electric Amazonian eel, Electrophorus electricus (Teleostei, Gymnotiformes), from the Brazilian rivers Amazon and Araguaia

A karyotype analysis of the electric eel, Electrophorus electricus (Teleostei, Gymnotiformes), a strongly electric fish from northern South America, is presented. Two female specimens were analyzed, one from the Amazon River and one from the Araguaia River. The specimens had a chromosomal number of 2n = 52 (42M-SM + 10A). C-bands were present in a centromeric and pericentromeric position on part of the chromosomes; some interstitial C-bands were also present. Heteromorphic nucleolus organizer regions (NORs) were detected in two chromosome pairs of the specimen from the Amazon River. The chromosome number and karyotype characteristics are similar to those of other Gymnotidae species. The genera Electrophorus and Gymnotus are positioned as the basal lineages in the Gymnotiformes phylogeny.

Theileria electrophorin.sp., a parasite of the electric eel Electrophorus electricus (Osteichthyes: Cypriniformes: Gymnotidae) from Amazonian Brazil

The name Theileria electrophori n.sp. is proposed for a small parasite described in the erythrocytes of the electric eel, Electrophorus electricus, from Amazonian Brazil. Division of the organism in the erythrocyte produces only four bacilliform daughter cells which become scattered in the host cell, without a cruciform or rosette-shaped disposition. Exoerythrocytic meronts producing a large number of merozoites were encountered in Giemsa-stained impression smears of the internal organs, principally in the liver, and are presumably the source of the intraerythrocytic forms of the parasite. This developmental pattern is characteristic of piroplasms within the family Theileriidae, where the author considers the parasite of E. electricus to most appropriately belong. It effectively distinguishes the organism from the dactylosomatid parasites Babesiosoma Jakowska and Nigrelli, 1956 and Dactylosoma Labbé, 1894 also found in fishes. This appears to be the second report of Theileria Bettencourt, Franca and Borges, 1907 in a fish.

Choline acetyltransferase detection in normal and denervated electrocyte from Electrophorus electricus (L.) using a confocal scanning optical microscopy analysis

Acetylcholine is the neurotransmitter responsible for the transmission of impulses from cholinergic neurons to cells of innervated tissues. Its biosynthesis is catalyzed by the enzyme Choline acetyltransferase that is considered to be a phenotypically specific marker for cholinergic system. It is well known that the regulation of Choline acetyltransferase activity under physiological and pathological conditions is important for development and neuronal activities of cholinergic functions. We observed the distribution of Choline acetyltransferase in sections from the normal and denervated main electric organ sections of Electrophorus electricus (L.) by immunofluorescence using a anti-Choline acetyltransferase antibody. The animals were submitted to a surgical procedure to remove about 20 nerves and after 30 and 60 days, they were sacrificed. After 30 days, the results from immunohistochemistry demonstrated an increase on the Choline acetyltransferase distribution at denervated tissue sections when compared with the sections from the normal contralateral organ. A very similar labeling was observed between normal and denervated tissue sections of the animals after 60 days. However, Choline acetyltransferase activity (nmolesACh/ min/ mg of protein) in extracts obtained from electrocyte microsomal preparation, estimated by Fonnun's method (Fonnun 1975), was 70 per cent lower in the denervated extracts.

The cytoskeleton of the electric tissue of Electrophorus electricus, L

The electric eel Electrophorus electricus is a fresh water teleost showing an electrogenic tissue that produces electric discharges. This electrogenic tissue is distributed in three well-defined electric organs which may be found symmetrically along both sides of the eel. These electric organs develop from muscle and exhibit several biochemical properties and morphological features of the muscle sarcolema. This review examines the contribution of the cytoskeletal meshwork to the maintenance of the polarized organization of the electrocyte, the cell that contains all electric properties of each electric organ. The cytoskeletal filaments display an important role in the establishment and maintenance of the highly specialized membrane model system of the electrocyte. As a muscular tissue, these electric organs expresses actin and desmin. The studies that characterized these cytoskeletal proteins and their implications on the electrophysiology of the electric tissues are revisited.

Comparative Studies on the Expression of CD5 B-Lymphocytes in Exprimental Autoimmune Masthenia Gravis (EAMG) and in Human Myasthenia Gravis

BACKGROUND: A human B-cell subpopulation which is identifiable by the expression of cell surface antigen Leu-1 (CD5) is known to be responsive for the antoantibody secretion. The exprimental autoimmune myasthenia gravis(EAMG) could be induced in animals by injecting AChR from electric eel and had the same clinical and pathophysiological characteristics with human myasthenia gravis(MG). The authors performed the study to compare the frequncy of CD5 positive B-lymphocytes in EAMGs with those in human MGs and to understand whether the EAMG showed the similar immunological feature as in human MG. METHOD: For EAMG the 50ug AChR from Torpedo Marmorata with Freund's adjuvant were injected to Lewis rats of 150-200mg three times. The CD5 positive B-lymphocytes from peripheral blood were double stained by the monoclonal PE conjugated anti-CD5 and FITC conjugated anti-rat CD45 antibodies in the EAMGs and by the PE conjugated ani-Leu-11(CD5) and FITC conjugated anti-human Leu-12(CD19) antibodies in human MGs. The expression of positive CD5 positive B-lymphocytes were calculated by the fluorescent activated cell sorter(FACS). RESULTS: The mean CD5 positive B-lymphocytes expression in four EAMGs was 15.05% with ranging from 10.2% to 20,0%, which was increased compared with those in control rats. The mean frequency of CD5 positive B-lymphocytes were 25.2+/-15.05% in human MG(N=25) and 16.0+/-13.5% in normal controls (N=20) respectively, which did not show any significant difference (P=0.08). However the expression of CD5 positive B-lymphocytes in human MGs was significantly correlated with the titer of anti-AChR antibody (P=0.04). CONCLUSION: The increased expression of CD5 positive B-lymphocytes might be associated with the EAMG pathomechansms, but their expression only showed possible correlation with the anti-AchR antibody titer with minimal role in pathogenetic process of human MG. Therefore it would be suggested that immunological process of EAMG (acute form of MG) be a little different from that of human MG, chronic form.

Structural and cytochemical localization of the endoplasmic reticulum in the electrocyte of electrophorus electricus

Vesículas com vários diâmetros variando entre 0.06 e 0.6 micronm e localizadas em torno do núcleo, bem como na proçäo mais periférica, foram observadas no electrócito do peixe elétrico Electrophorus electricus. Tais vesículas foram consideradas como componentes de retículo endoplasmático do eletrócito uma vez que observaçöes citoquímicas demonstraram a presença de glicose-6-fosfatase na membrana dessas vesículas. Esta idéia é reforçada por resultados obtidos com o uso da técnica do pirantiminiato de potássio e análise espectroscópica de elétrons, que mostrou a presença da Ca++ na membrana das vesiculas

Modification of electrocyte membrane lipid composition induced by denervation

1. We determined the effect of denervation on the lipid composition of the main electric organ and electrocyte postsynaptic membrane vesicles of Electrophorus electricus. 2. Lipid extracts of whole electric organ contain mainly cholesterol, triglycerides, phosphatidylcholine and phosphatidlethanolamine. After 30 days of denervation, the lipid composition of whole electric organ did not change appreciably. 3. Lipid extracts of the membrane vesicles were similar, except that they contained mainly free fatty acids rather than triglycerides. After 30 days of denervation, cholesterol concentration was increased and phsopholipids were decreased in the membrane fraction, with higher relative concentrations of phosphatidylethanolamine and cerebrosides. 4. These results suggest that electrocyte membrane fluidity and permeability will change after 30 days of denervation

Histochemical detection of creatine kinase ion the electrocyte of Electrophorus electricus (L.)

Detection of creatine kinase, which catalyzes the conversion of ADP and phosphocreatine to ATP and creatine, was performed an the electrocyte of Electrophorus electricus (L.) using a histoenzymological method based on the formation of blue colored formazan. The results indicate that the enzyme is mainly located within the cytoplasm of the electrolyte