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Biomedical subjects

A S Penn

Publications and source records attributed to A S Penn.

At least 37 records · Page 2Linked to original sources
PubMed1984

Alpha-bungarotoxin binding to the myotome and choline acetyltransferase activity in the rabbit embryo.

We have previously found incomplete sarcomeres and acetylcholinesterase activity in the myoblasts of the myotome of the rabbit at day 13 of gestation. We now report that an acetylcholine (ACh)-synthesizing enzyme and the nicotinic receptor are present at this stage as well. A study of the myotome using [125I]alpha-bungarotoxin shows that the mononucleated myoblasts have alpha-bungarotoxin binding sites before they migrate away to form multinucleated myotubes. Choline acetylcholinesterase activity and/or a different ACh-synthesizing enzyme are found at early stages of development, even before the spinal nerve has formed. An ACh-synthesizing enzyme is present in the notochord, a neural tube-dorsal root ganglion preparation, as well as in rows of myotomes separated from the latter preparation. Assays of isolated myotomes with very little adherent mesenchyme indicate that the enzyme is located either within the myotome or in its immediate vicinity. Cholinergic components, therefore, are associated with the mononucleated myoblasts of the myotome before they fuse to form myotubes and before they receive their permanent innervation.

Animals↗
PubMed1984

Augmented anti-acetylcholine receptor response following long-term penicillamine administration.

Because of the association of D-penicillamine (DP) therapy with myasthenia gravis, we have studied long-term DP treatment in five inbred strains of mice with doses comparable to those used in patients with rheumatoid arthritis. No clinical weakness or anti-acetylcholine receptor (AChR) antibody developed with up to 6 months of treatment, but augmented responses did occur to challenge with purified AChR in adjuvant. Anti-AChR antibody titers in C57BL/6 and C3H/He mice were significantly higher after challenge with AChR in DP-treated than in control mice. Augmented anti-AChR titers were not seen in strain A mice, but after 6 months of DP treatment increased susceptibility developed to the induction of experimental autoimmune myasthenia gravis. Nine weeks after challenge with purified AChR, 10 of 11 mice developed clinical weakness, leading to death in 6. Results of edrophonium testing were positive in 5 of 6 mice, and electrophysiological abnormalities were demonstrated in 3 of the surviving mice. Long-term DP treatment is associated with augmented anti-AChR antibody responses in C3H/He and C57BL/6 mice, and increased susceptibility to experimental autoimmune myasthenia gravis in strain A mice.

Animals↗
PubMed1984

Myasthenia gravis: determinants for independent ventilation after transsternal thymectomy.

We evaluated the respiratory function of 32 patients with myasthenia gravis who had transsternal thymectomy. Preoperative clinical, pulmonary function, and respiratory muscle pressure data were submitted to stepwise logistic regression analysis to identify preoperative factors that correlated with duration of supported ventilation after surgery. Ten patients (31%) had postoperative supported ventilation for more than 3 days. The duration of ventilatory support correlated most closely with maximal static expiratory pressure (r = 0.714, p less than 0.001). Expiratory weakness, by reducing cough efficacy, seems to be the main determinant that predicts need for longer postoperative supported ventilation.

Adolescent↗
PubMed1983

Prognosis of ocular myasthenia.

A retrospective study of 108 patients with myasthenia gravis who had solely ocular symptoms and signs at onset was carried out to identify factors influencing prognosis. Increasing duration of pure ocular myasthenia was associated with a decreasing risk of late generalized symptoms; only 9 (15%) of the observed generalizations occurred after more than 2 years of solely ocular symptoms. Increasing age at onset was associated with greater risk of respiratory crisis or death caused by myasthenia, whereas patients younger at onset had a greater chance of a benign outcome. Neither systemic curare tests nor responses to repetitive nerve stimulation had prognostic value.

Adolescent↗
PubMed1982

Anti-idiotypic route to anti-acetylcholine receptor antibodies and experimental myasthenia gravis.

trans-3,3'-Bis[alpha-(trimethylammonio)methyl]azobenzene bromide (BisQ) is a potent agonist of the acetylcholine receptor (AcChoR) of Electrophorus electricus. BisQ is highly constrained, suggesting that its structure is complementary to the combining site of the AcChoR when the latter is in its activated state. Antibodies produced in rabbits to a conjugate of bovine serum albumin and a derivative of BisQ mimicked the binding characteristics of the AcChoR with respect to the order of binding of a variety of agonists and to the preferred recognition of decamethonium ion (an agonist) over hexamethonium ion (an antagonist). Immunization of three rabbits with purified anti-BisQ yielded antisera having binding characteristics of anti-AcChoR in that, by complement fixation and enzyme immunoassay, crossreactions with receptor preparations from rat, Torpedo, and eel could be demonstrated in sera of all three rabbits immunized. Two of the three rabbits showed signs of muscle weakness similar to that seen after immunization with the AcChoR. One of the rabbits was injected intramuscularly with neostigmine and showed temporary improvement. Another showed post-tetanic exhaustion of hind-limb muscles after stimulation of the sciatic nerve at 50 Hz. Antibodies reactive with the AcChoR, therefore, were elicited by immunization with an antibody to a potent ligand of the AcChoR without the necessity of isolating the receptor itself. A similar mechanism may play a part in the etiology of at least some autoimmune diseases in which antibodies to various other receptors are involved.

Animals↗
PubMed1982

Penicillamine-induced myasthenia gravis: effects of penicillamine on acetylcholine receptor.

Autoimmune diseases, including myasthenia gravis, occur in patients treated with D-penicillamine. Because D-penicillamine might induce autoantibodies by the mechanism of antigenic alteration, we studied the reaction of D-penicillamine with purified acetylcholine receptor from Torpedo californica. We found that brief exposure to D-penicillamine resulted in its covalent attachment to two receptor subunits, alpha (40,000 daltons) and gamma (59,000 daltons), presumably by reduction and formation of mixed disulfides. Furthermore, D-penicillamine treatment resulted in a dramatic modification of the equilibrium acetylcholine binding properties of both purified receptor and receptor-rich membrane fragments.

Acetylcholine↗
PubMed1982

Severe dystonia and myoglobinuria.

Myoglobinuria may follow extreme muscular exertion or disorders that cause muscle necrosis. Dystonia has not been implicated previously. We studied an 8-year-old boy of non-Jewish, Mexican-American descent with autosomal-dominant dystonia musculorum deformans who developed rapidly progressive and severe generalized dystonia, hyperpyrexia, myoglobinuria, and renal failure. Curarization was required. Transient improvement was achieved with tetrabenazine and baclofen, but bilateral thalamotomy was then performed. Patients with severe dystonia should be observed for evidence of myoglobinuria.

Child↗
PubMed1981

Antiacetylcholine receptor antibody in neonatal myasthenia gravis.

Maternal titers to antiacetylcholine receptor antibody (anti-AChR Ab) were higher in two mothers with myasthenia gravis (MG) who had infants with neonatal MG than the nearly normal values in two mothers with MG who had unaffected infants. In one unaffected infant, another IgG antibody crossed the placenta, but an IgM antibody did not. In neonates there seems to be a correlation between the concentration of anti-AChR Ab and the presence and severity of the neonatal syndrome. The absence of fetal symptoms of MG and the delayed onset or worsening of some cases of neonatal MG may be due to high fetal levels of alpha-fetoprotein and its decline in concentration in infants after birth.

Acetylcholine↗
PubMed1981

Plasma cell dyscrasia and peripheral neuropathy: identification of the myelin antigens that react with human paraproteins.

In some cases of polyneuropathy and plasma cell dyscrasia, the monclonal antibodies react with human peripheral nerve myelin. To identify the myelin antigens involved, we separated the proteins of human central and peripheral nerve myelin by polyacrylamide gel electrophoresis, transferred the proteins onto nitrocellulose sheets, and used an immunoenzymatic technique to detect the reactive antigens. Serum IgM but not IgG from three patients with neuropathy and complement-fixing anti-human myelin IgM paraproteins immunostained a protein of approximately 100,000 daltons in human peripheral nerve myelin and a protein or closely migrating proteins of similar size in human central nervous system myelin. In a fourth patient, both IgM and IgG immunostained the antigen. Immunostaining was specific for the paraprotein light chain type, and absorption of the patients' sera with human peripheral nerve myelin eliminated the reaction with the central nervous system proteins. No reaction was seen with rabbit peripheral nerve myelin or with membranes prepared from human myotubes, human T cells, or human fibroblasts. Control sera from six patients with neuropathy and IgM paraproteins that did not react with myelin, from four patients with IgM paraproteins but no neuropathy, and from three normal subjects did not immunostain myelin.

Antibodies, Monoclonal↗
PubMed1981

Thymic abnormalities: antigen or antibody? Response to thymectomy in myasthenia gravis.

The therapeutic value of thymectomy for myasthenia is still questioned although it retains an important place among management modalities that strive for sustained remission. Questions derive from uncertainty as to appropriate timing, variable extent of resection and quantitation of response. Forty-seven patients, followed one to seven years, underwent an extended transsternal or combined transcervical-transsternal procedure with anterior mediastinal exenteration. Sixteen have been in complete remission from six months to six years, four are asymptomatic on occasional pyridostigmine and eight are significantly improved. Evaluation of thymic pathology (hyperplasic, involuted areas, and thymoma) included a search for thymic myoid cells by fluorescence cytochemistry. Antibodies to acetylcholine receptor present in 38 of 43, decreased post-operatively to normal in four, by 50% to 80% in 14, by 20 to 50% in three and were unchanged in 14. Most remissions occurred in young women with noninvoluted hyperplastic glands and variably high anti-AChR titers which dropped toward normal in seven of 15. These results encourage us to utilize this procedure routinely.

Adolescent↗
PubMed1981

Mucolipidosis II (I-cell disease): studies of muscle biopsy and muscle cultures.

Muscle cultures from a patient with I-cell disease showed the characteristic morphologic and biochemical abnormalities previously observed in cultured fibroblasts. At early stages of myoblast growth, there were numerous inclusions. Biochemically, the intracellular activities of beta-galactosidase, beta-hexosaminidase, and alpha-mannosidase were reduced to 1, 14, and 5%, respectively, of control values, and this was accompanied by elevated levels of beta-hexosaminidase and alpha-mannosidase in the culture medium. Cultures from the patient did not fuse as well as controls; however, when well-developed myotubes possessing distinct cross-striations were present, these no longer had inclusions. In the muscle biopsy from this patient, only beta-galactosidase was decreased to approximately 50% of the mean control value whereas beta-hexosaminidase and alpha-mannosidase activities were increased as compared to controls. These data suggest that the I-cell mutation is expressed during early myogenesis but not in well-differentiated myotubes or mature muscle fibers.

Biopsy↗
PubMed1981

Complement-fixing antiperipheral nerve myelin antibodies in patients with inflammatory polyneuritis and with polyneuropathy and paraproteinemia.

Serum from patients with peripheral neuropathies was tested for antiperipheral nerve myelin antibodies by complement fixation. Antibody activity was detected in 5 of 20 patients with acute or chronic remitting polyneuritis and in 4 of 20 patients with polyneuropathy and paraproteinemia but not in patients with other types of neuropathy, neurologic disease, or immunologic disease. In three patients with IgM paraproteinemia, the complement-fixing activity resided in the IgM fraction; in one patient with chronic inflammatory polyneuritis, antibody activity resided in the IgG fraction. In the inflammatory polyneuropathies, antibody titers did not always correlate with disease activity. Sera from patients with remitting polyneuropathies reacted with either human or rabbit peripheral nerve myelin, but sera from patients with paraproteinemia reacted only with human myelin.

Animals↗
PubMed1980

Heterozygous C2-deficiency and myasthenia gravis.

Complement deficiency states in myasthenia gravis (MG) have not been reported previously. We describe a 19-year-old woman with typical MG and heterozygous C2 deficiency, along with HLA typing of the patient and her immediate family.

Acetylcholine↗
PubMed1979

Isolation of influenza virus from muscle in myoglobinuric polymyositis.

We report the first isolation of influenza virus from muscle in a man with myoglobinuria and acute polymyositis. Influenza virus was isolated from cultures of Madin Darby bovine kidney and primary rhesus monkey kidney cells inoculated with muscle homogenates in the presence of trypsin; the virus was identified by neutralization and hemagglutination inhibition studies using influenza B/Lee antiserum. Viral plaque assay was performed with Madin Darby canine cells. Viral antigen was also detected by specific immunofluorescence in muscle, and myxovirus-like particles were seen in subsarcolemmal vacuoles by electronmicroscopy. The pathologic findings were similar to those of childhood dermatomyositis, except for a large proportion of necrotic muscle fibers. The evidence suggests that the pathogenesis of influenzal polymyositis in this patient involved direct viral infection of muscle.

Acute Disease↗