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Biomedical subjects

C John

Publications and source records attributed to C John.

At least 73 records · Page 4Linked to original sources

Enhancement of immunostimulating and immunotherapeutic effect of BCG vaccines using listerial endotoxin-like substances.

On the basis of experience with the immunomodulating effect of the endotoxin-like component of Listeria monocytogenes, designated factor Ei, the time parameters concerning the onset and duration of hypersensitivity induced by listeriae, mycobacteria and their components were compared. Their differences, just like different mechanism of their effect, following their simultaneous and repeated administration, furnish means of significantly enhancing the anti-tuberculosis and anti-tumor effect of strong BCG vaccines in animal experiments. This enhancement of effect makes it possible to lower the number of BCG doses otherwise required to produce the same or similar results.

Animals↗

Changes in the migratory activity of polymorphonuclear leukocytes after administration of Freund's adjuvant.

Spontaneous and chemotactic activity of polymorphonuclear leukocytes, obtained from the peritoneal cavity, was studied after administration of complete and incomplete Freund's adjuvant to rabbits at intervals of 18-26 d after adjuvant injection. Whereas injection of both complete and incomplete adjuvant increased spontaneous migration of rabbit polymorphonuclear leukocytes, the migration directed by the chemotactic signal, induced in fresh serum by E. coli endotoxin, was decreased. The chemotaxigenic activity of two factors, isolated from cell walls of Listeria monocytogenes was also tested: factor Ei (its most potent component is lipopolysaccharide) and a purified phenol extract of lipopeptidopolysaccharide nature.

Adjuvants, Immunologic↗

At least three sequential steps are involved in the tetanus toxin-induced block of neuromuscular transmission.

Tetanus toxin causes a block of the neuromuscular transmission. The kinetic aspects of the block were studied in vitro on the mouse phrenic nerve-hemidiaphragm exposed to toxin (1 microgram/ml). 1. The toxin action on the nerve ending involves three sequential steps: binding, "translocation" and paralysis. 2. Diffusion and binding of tetanus toxin molecules to the presynaptic membrane is complete in about 60 min. The binding step is irreversible, independent of transmitter release and of the temperature. Tetanus antitoxin, however, inactivates the bound toxin molecules. 3. After a second step which is probably due to a "translocation" of the toxin molecules into or through the presynaptic membrane the antitoxin molecules are now ineffective to prevent the toxin-induced inhibition of transmitter release. This so called "translocation" step requires transmitter release and therefore depends strongly on the frequency of nerve stimulation. 4. The paralytic step does not depend on the transmitter release. It, however, depends strongly on temperature with a break in the Arrhenius-plot around 33 degrees C which suggests the involvement of a phase transition rather than of an enzymatic activity of the toxin.

Animals↗

Resistance to Mycobacterium tuberculosis H37Rv infection induced by Listeria and mycobacterial lipids.

The avirulent strain Listeria monocytogenes (Welshimer) induced upon a single injection 4 weeks prior to challenge with Mycobacterium tuberculosis H37Rv resistance in guinea-pigs, which was manifested by a significant decrease of spleen weight and Feldman's index in immunized animals. The degree of resistance was dependent on the immunizing dose and time of administration. Repeated high doses of Listeria yielded only a low or no effect. Further increase of resistance was obtained using the BCG lipids; however, stimulation of resistance with listeria lipids was not successful and, finally, Freund's incomplete adjuvant was significantly effective in the Feldman index only. The BCG lipids, extracted with ethanol, which contained nitrogen and water-soluble substances, induced a significant resistance against M. tuberculosis infection. The chloroform-methanol BCG lipids were also effective, however, significantly less than the ethanol-extracted material. The listeria factor Ei itself or together with Freund's incomplete adjuvant possessed only low effectiveness against mycobacterial infection. However, if injected together with ethanol-extracted BCG lipids, it produced a significant degree of resistance which was higher than that induced by lipids only. The degree of resistance was comparable with the effect of living BCG strain which served as a source of isolated lipids.

Animals↗