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D Mochly-Rosen

Publications and source records attributed to D Mochly-Rosen.

81 records · Page 5Linked to original sources
PubMed1985

Antigenic specificity of acetylcholine receptor in developing muscle. Studies with monoclonal antibodies.

Monoclonal antibodies (mcAbs) elicited against the nicotinic acetylcholine receptor (AChR) from Torpedo, were used to follow antigenic changes in AChR during muscle development. Newborn rat muscle and denervated mouse muscle were used as sources of extrajunctional AChR; adult innervated rat and mouse muscle were used as sources of junctional AChR. Most of the mcAbs tested reacted preferably, but not exclusively with extrajunctional AChR (EJR), as compared to junctional AChR (JR). None was found to react with only one of the two forms of AChR. We conclude that the anti-AChR monoclonal antibodies used in this study detect antigenic determinants which are shared by EJR and JR, but which probably undergo structural changes during muscle development.

Animals↗
PubMed1983

An anti-acetylcholine receptor monoclonal antibody cross-reacts with phosvitin.

Rabbit and mouse anti-Torpedo acetylcholine receptor antibodies cross-reacted partially with the highly phosphorylated protein, phosvitin. We have selected an anti-Torpedo acetylcholine receptor monoclonal antibody which binds specifically to phosvitin; this binding is inhibited by acetylcholine receptor. These findings suggest that a phosphorylated amino acid residue may be a part of the determinant on the acetylcholine receptor recognized by this monoclonal antibody.

Animals↗
PubMed1983

Interaction of monoclonal antibodies to Torpedo acetylcholine receptor with the receptor of skeletal muscle.

Several monoclonal antibodies (mcAbs) elicited against the nicotinic acetylcholine receptor (AChR) from Torpedo react also with skeletal muscle AChR. Such mcAbs were used to define antigenic determinants on muscle AChR and to elucidate their effect on muscle AChR functions. Primary chick muscle cultures were used as a model for skeletal muscle. Of the four mcAbs studies only mcAb 5.5, which is directed against the cholinergic site in Torpedo AChR, blocks the binding of alpha-bungarotoxin (alpha-Bgt) to AChR in chick muscle cultures and inhibits carbamylcholine-induced sodium transport in these cells. The interaction of mcAb 5.5 with the cholinergic site on muscle AChR demonstrates the conservation of this site. Two mcAbs, 5.5 and 5.34, each of a different antigenic specificity but both directed against conformation-dependent antigenic determinants, accelerate the degradation of AChR in muscle cultures. From the reactivity of the various mcAbs with Triton-solubilized and membranous AChR it appears that there are some antigenic differences between the detergent solubilized and membranous forms of the receptor.

Animals↗
PubMed1983

Monoclonal antibodies modify acetylcholine-induced ionic channel properties in cultured chick myoballs.

Monoclonal antibodies directed against the cholinergic binding site of the acetylcholine receptor were found to alter the ion channel properties in cultured chick "myoballs." Time and dose dependent reduction in acetylcholine sensitivity was observed. Noise analysis experiments indicated a decrease in the mean single channel conductance and an increase in the mean single channel open time.

Acetylcholine↗
PubMed1981

Monoclonal anti-acetylcholine-receptor antibodies directed against the cholinergic binding site.

We have isolated 32 hybridoma cell lines producing monoclonal antibodies against the acetylcholine receptor from Torpedo californica. One of these lines, designated 5.5.G.12, secretes antibodies which are directed against the cholinergic binding site of the acetylcholine receptor. This specific antibody blocked the binding of alpha-bungarotoxin to the acetylcholine receptor. The binding of monoclonal antibody 5.5.G.12 to acetylcholine receptor was inhibited by alpha-neurotoxins and by other cholinergic ligands in accordance with their affinities to the nicotinic acetylcholine receptor. None of the other monoclonal antibodies obtained inhibited the binding of alpha-bungarotoxin to acetylcholine receptor, nor was their binding to the acetylcholine receptor inhibited by cholinergic ligands. The monoclonal antibody elicited against the binding site of Torpedo acetylcholine receptor bound also to acetylcholine receptors of various species and organs, demonstrating the wide structural homology between the cholinergic sites of various acetylcholine receptors.

Animals↗
PubMed1981

Molecular aspects of experimental autoimmune myasthenia gravis.

Structure and function studies on acetylcholine receptor (AChR) were attained by studying various derivatives of the receptor molecule, by analysis of monoclonal antibodies, and by investigating the possible structural relationship between AChR and the thymus. Pharmacologically inactive denatured AChR preparation does not induce myasthenia in rabbits, although it elicits antibodies that cross-react with the intact receptor. Denatured AChR has both preventive and therapeutic effects on experimental autoimmune myasthenia gravis. Mild tryptic digestion of AChR does not abolish the pharmacological specificity and myasthenic activity of the receptor. Trypsinated AChR, which on SDS gel electrophoresis shows one major band with a molecular weight of 27,000, represents an active receptor derivative with a relatively low structural complexity. Monoclonal antibodies against defined determinants of AChR were elicited and characterized. One monoclonal antibody line is directed against the cholinergic binding site. Experiments demonstrating that thymic lymphocytes bear a surface antigen that cross-reacts with AChR are described.

Animals↗
PubMed1980

Immune regulation of experimental myasthenia.

Experimental autoimmune myasthenia gravis (EAMG) is an appropriate model for studying the molecular origin, immunological mechanism and regulation of myasthenia gravis. Several approaches are being utilised for the regulation of the immune response to AChR and for immunosuppression of EAMG: Corticosteriods and azathioprine can suppress EAMG concomitantly with suppression of immune responses to AChR. High dose cyclophosphamide treatment in mice facilitates the onset of EAMG and results in a selective suppression of the humoral response to AChR whereas the cellular response is enhanced. Specific immunosuppression of EAMG is achieved by using a nonmyasthenic, denatured AChR preparation which cross reacts with the intact receptor. Various degradations and modifications of AChR are being performed in order to identify the smallest molecular entity responsible for the myasthenic activity of AChR. Studies on specific monoclonal antibodies, anti-idiotypes, and on the effect of measles virus on EAMG are being described and their possible significance in regulating myasthenia are being discussed.

Acetylcholine↗