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Biomedical subjects

S Fuchs

Publications and source records attributed to S Fuchs.

At least 325 records · Page 18Linked to original sources

Myasthenia gravis and acetylcholine receptor. Effect of steroids in clinical course and cellular immune response to acetylcholine receptor.

Lymphocytes from patients with myasthenia gravis (MG) were transformed when cultured in vitro with an acetylcholine receptor fraction extracted from the electric organ of an electric eel. Marked diminution of the cellular response to acetylcholine was shown in patients who improved clinically with prednisone treatment. The transient clinical deterioration during the first days of prednisone treatment was accompanied by a transient increase in lymphocyte response. These findings that an in vivo sensitization of lymphocytes to self-acetylcholine receptor may occur in MG, and that a cell-mediated autoimmune mechanism may be important in the pathogenesis of the neuromuscular block. The present observations indicate that prednisone provides a measure of immunosuppression in MG. The transient clinical deterioration during the first days of prednisone therapy may reflect an enhancement of cell reactivity by this drug.

Acetylcholine↗

The effect of the thymus-independent antigens, collagen and synthetic collagen-like polypeptide, on the requirement of cell cooperation in the immune response to thymus-dependent antigens.

The effect of thymus-independent antigens on the need for cell cooperation in the immune response to thymus-dependent antigens was investigated. Irradiated recipient mice transplanted with either bone marrow cells or a mixture of bone marrow and thymus cells, were immunized with the thymus-independent antigen (Pro-Gly-Pro)n covalently conjugated to the thymus-dependent ovalbumin, or with a mixture of (Pro-Gly-Pro)n and ovalbumin. In both cases an effective response towards ovalbumin was observed in the absence of thymus cells as was found for the thymus-independent (Pro-Gly-Pro)n. The same effect on ovalbumin was demonstrated when a mixture of the thymus-independent collagen and ovalbumin was used for immunization. On the other hand, when irradiated reconstituted mice were immunized with a mixture of ovalbumin and the thymus-dependent gelatin, which is the denatured product of collagen, cell-to-cell cooperation was required for an immune response to both immunogens. The effect of (Pro-Gly-Pro)n and collagen on the response to the thymus-dependent ovalbumin in vivo was observed in in vitro experiments using sheep red blood cells (SRBC) as the immunogen as well. In the presence of reduced and carboxymethylated (RCM) Ascaris collagen and (Pro-Gly-Pro)n, nude spleen cells could produce significant numbers of plaque-forming cells towards SRBC. Thus, (Pro-Gly-Pro)n and collagen can deliver the signal required to stimulate B cells to produce antibody towards thymus-dependent antigens in the absence of T cells. In contrast to the results with (Pro-Gly-Pro)n and collagen, the thymus-independent synthetic polypeptide poly(DTyr, DGlu-)-poly(DPro)--poly(DLys) did not affect the requirement for cell cooperation of the thymus-dependent immunogens, ovalbumin and SRCB. It thus appears that the ability to substitute for T cells for antibody production towards thymus-dependent immunogens is not a general characteristic of thymus-independent antigens.

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Differential cytotoxic acitivity of anticollagen serum on rat osteoblasts and fibroblasts in tissue culture.

Rat skin fibroblasts grown in tissue culture were lysed by anti-rat-tail collagen serum and antibodies to the ordered collagen-like synthetic polymer (Pro-Gly-Pro)-n. This cytotoxic effect is complement-dependent and occurs only if the fibroblasts were pretreated with trypsin. These anti-sera have very little cytotoxicity on cultured rat osteoblasts. This differential cytotoxicity is not due to differential binding of anticollagen serum to the cells. Both osteoblasts and skin fibroblasts bind the anticollagen serum as was demonstrated by fluorescent immunoglobulin.

Animals↗

Immunological relationship between acetylcholine receptor and thymus: a possible significance in myasthenia gravis.

A defined immunological cross-reaction was observed between acetylcholine receptor fraction from the electric eel, Electrophorus electricus, and two calf thymus fractions. The cross-reaction was demonstrated on the cellular level by means of the lymphocyte transformation technique, and on the humoral level, by means of the microcomplement fixation assay. In the human disease myasthenia gravis both acetylcholine receptor at the neuromuscular junction and the thymus are affected, probably by an autoimmune mechanism. The immunological cross-reaction between acetylcholine receptor and thymic components may explain the association between endplate and thymus disorders in myasthenia gravis.

Acetylcholine↗

The nature of murine immune response to nucleic acids.

The antibody response of mice to nucleic acids appears to be genetically regulated, and may show varying patterns. SJL/J mice and AKR/Cu mice are high responders to denatured DNA complexed with MBSA and produce 7S as well as 19S antibodies. DBA/2 mice respond with low titers to this immunogen which consists of 19S antibody exclusively. C57BL/6 mice are high responders to denatured DNA, but produce only 19S antibodies. Denatured DNA-MBSA is immunogenic when injected without complete Freund's adjuvant, thereby suggesting that this antigen might be thymus independent. The pattern of immune responses of some strains to the polyribonucleotides poly(I)-poly(C) and poly(A)-poly(U) is opposite to that observed with denatured DNA. Thus, DBA/2 mice are high responders and SJL/J mice are low responders. However, the low responders SJL/J mice produce 7S as well as 19S antibody which suggests that different mechanisms operate for the regulation of immune responses to the two types of nucleic acids. Whereas no antibody is elicited upon immunization with DNA in the absence of a carrier protein, poly(A)-poly(U) and poly(I)-poly(C) are immunogenic when injected without MBSA. Immunization with complexes of the polyribonucleotides and MBSA enhanced the responses to these immunogens; however, the strain differences were not completely abolished. Poly(A)-poly(U) did not enhance the low immune responses of DBA/2 mice to denatured DNA when injected i.v. following immunization with the DNA-MBSA. However, simultaneous immunization of DBA/2 and SJL/J mice with poly(A)-poly(U) and denatured DNA-MBSA resulted in high antibody titers to both immunogens in either mouse strain.

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[Colony defence of Asian honey bees].

Colony Defence in Asian Honey Bees. 1. In Ais cerana, Apis dorsata and Apis florea a defence behaviour (Körperschütteln) can be released by the approach of flying insects. Films of Apis cerana colonies exhibiting this behaviour were made and anaylysed. 2. Körperschütteln "could not be released by various mechanical and chemical" stimuli. Only the movement of a dark object before light background was effective in releasing this behaviour. 3. The optimal angular velocity of the dark object when moved on a moving disk was between 80 degrees to 250 degrees per sec. The optimal size for stimulation was between 5 degrees and 12 degrees (visual angle). 4. The stimulatory effect was not greatly influenced by the shape of the dark object. 5. Continued stimulation over a 90 min period resulted in 80% reduction in the number of responding bees. 6. The colony's ability to discriminate between returning forager bees and other flying insects is discussed.

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Cellular immune response to acetylcholine receptor-rich fraction, in patients with myasthenia gravis.

Lymphocytes from patients with myasthenia gravis were stimulated when cultured in vitro with an electric eel extract enriched in acetylcholine receptor. No stimulation was observed with other antigens from nerve or muscle origin. Lymphocytes from non-myasthenic patients showed no response to any of these antigens. These findings suggest that an in vivo sensitization of lymphocytes to self acetylcholine receptor may occur in myasthenia gravis. The presence of sensitized lymphocytes, probably resulting from an autoimmune mechanism, might be an important factor in the pathogenesis of the neuromuscular block in this disease.

Acetylcholine↗

Fractionation of functional lymphocytes sensitized to basic encephalitogen on derivatized collagen and gelatin gels.

The lymph node cells of basic encephalitogen (BE)-sensitized guinea pigs were fractionated on derivatized collagen and gelatin gels. The population of cells specifically reactive to this antigen can be isolated from derivatized gelatin gels and retain their viability and functionality as assayed in vitro. The specific binding of BE-sensitized cells to BE-derivatized gels comprised between 1 and 2% of the cells applied per plate. The ratio of sensitized cells bound to non-sensitized cells bound ranged between 4 and 6. The viability and functionality of adherent cells detached from collagen gels after enzymatic degradation were impaired. In contrast, the responses obtained with the adherent cell population released from the gelatin gels, by melting at 37 degrees C, were equal or greater than those of the original unfractionated lymph node cell cultures. Furthermore, it was possible to obtain a nonadherent cell population which was virtually completely depleted of the capacity to respond to the sensitizing antigen.

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