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Biomedical subjects

S Fuchs

Publications and source records attributed to S Fuchs.

At least 91 records · Page 5Linked to original sources

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

Production of a high affinity antiserum to benzodiazepines.

Antibodies specific for benzodiazepines were raised in rabbits by immunization with a conjugate of a benzodiazepine derivative, Ro 7-1986/1, with bovine serum albumin. The presence of anti-Ro 7-1986/1 antibodies in the sera was demonstrated by a radioimmunoassay using the radioligand [3H]flunitrazepam ([3h]FNZ). The antibodies displayed a high-affinity for [3H]FNZ (KD = 0.073 +/- 0.003 nM) and and cross-reacted with a broad spectrum of benzodiazepine derivatives. Benzodiazepine levels in samples of sera and urine of benzodiazepine-treated humans were determined. Due to the high sensitivity of the assay only minute volumes (microliter quantities) of body fluids are employed and, therefore, no extraction of the drugs is required. Nitrazepam and diazepam levels as low as 20 picograms can be easily observed. Intoxicating levels of benzodiazepines can be detected by a single measurement in less than 10 min. This radioimmunoassay is advantageous for pharmacokinetic studies, toxicological examinations and forensic medicine due to its high sensitivity, wide-range specificity and technical simplicity.

Animals

[Electroencephalographic and computer tomography findings in vascular epilepsy of ischemic origin].

143 patients with vascular epilepsy have been investigated, in whom generalised seizures were predominant (67%). 5% of the patients were younger than 30 years and 20% were between 30 and 50 years old. Pathological CT findings were seen in 78%. Focal lesions were most common particularly in patients with partial epileptic seizures as compared with those which had generalised seizures (p less than 0.05). In the EEG focal changes also dominated, but there was no significant difference in their occurrence with regard to patients with generalised or partial seizures. Epileptic potentials were observed in 17% of the patients with the emphasis on those with generalised epilepsies (p less than 0.05). Comparing EEG and CT in 69% of the patients concomitant pathological findings could be found. In patients with partial seizures there was a particularly good correlation between the focal changes in the EEG and lesions in the CT.

Adult

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

Consequences of premature weaning on the reproduction of mothers and offspring in laboratory mice.

A decrease of energy expenditure per offspring is expected to benefit the mother by increasing the number of offspring she can produce, and to inflict costs upon the young by decreasing their reproductive value. To evaluate the benefit-cost functions of shortened suckling times in house mice, the young were separated from their mothers prior to natural weaning. During two following litters of mothers and young, time of birth and numbers born were recorded. The impact of the resulting effects on the lifetime reproduction of mothers and young were evaluated by model calculations assuming population equilibrium, exponential population growth or exponential growth limited by population breakdowns.

Animals

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

Thymic lymphocytes bear a surface antigen which cross-reacts with acetylcholine receptor.

Acetylcholine receptor (AChR) is a major antigen in the neuromuscular disease myasthenia gravis and it is clear today that the basic defect in this disease is brought about by an autoimmune attack on acetylcholine receptors at the neuromuscular junctions. The involvement of the thymus and its role in myasthenia have been widely investigated but are still poorly understood. A high incidence of thymic abnormalities is observed in patients with myasthenia and thymectomy is beneficial in many cases. Immunological studies have demonstrated the presence of humoral as well as cellular immune responses towards thymic tissues in myasthenic patients. There were also some reports that animals immunized with thymic extracts develop a partial defect in neuromuscular transmission. In spite of all these observations, the nature and origin of the association between the thymus and the neuromuscular junction in myasthenia gravis are still not known. We have previously demonstrated an immunological cross-reactivity, both humoral and cellular, between a thymic component and AChR; such a cross-reactivity could provide a molecular explanation for the involvement of the thymus in myasthenia gravis. In this study, we demonstrate, by using immunofluorescence and radioimmunological techniques, that thymic lymphocytes bear a surface antigen which binds specifically to antibodies against nicotinic AChR and is thus defined as an 'AChR-like' antigen. A preliminary report of this study has been published.

Animals

Immunological cross-reactivity between electric-eel acetylcholinesterase and rat-tail-tendon collagen.

Immunological cross-reactivity between acetylcholinesterase from the electric organ of the electric eel and rat tail tendon collagen was examined both on the cellular and humoral levels. 1. Guinea pigs immunized with rat tail tendon collagen displayed a strong delayed-type skin reaction when tested with the elongated acetylcholinesterase preparation (i.e. 14-S + 18-S molecular forms). However, when the glubular 11-S enzyme was tested, almost no cross-reactivity was obtained. Similarly, guinea pigs immunized with 14-S + 18-S preparation exhibited skin sensitization to rat tail tendon collagen. 2. Using a radioimmunoassay, it was observed that 125I-labeled 14-S + 18-S acetylcholinesterase binds efficiently to rabbit antiserum elicited against rat tail tendon collagen, whereas 125I-labeled 11-S enzyme does not bind at all to this antiserum. Similar results were obtained by passive hemagglutination assay. The experiments suggest that 14-S + 18-S acetylcholinesterase, but not 11-S enzyme, which is devoid of the tail structure, has antigenic determinants in common with collagen from rat tail tendon.

Acetylcholinesterase