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Biomedical subjects

E Lederer

Publications and source records attributed to E Lederer.

At least 91 records · Page 5Linked to original sources

Enhancement of nonspecific immunity to Klebsiella pneumoniae infection by a synthetic immunoadjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine) and several analogs.

N-Acetylmuramyl-L-alanyl-D-isoglutamine and four other synthetic adjuvants that are structural analogs of part of the mycobacterial peptidoglycan monomer are shown to enhance the nonspecific immunity of mice infected by Klebsiella pneumoniae. These compounds are active by various routes, including oral administration; they are also effective when administered after challenge. Of the seventeen other analogs tested, none is able to increase significantly resistance to infection, although seven of these molecules are adjuvant-active in saline. Previous results have shown that in contrast to lipopolysaccharides, these synthetic adjuvants are devoid of immunogenicity, mitogenicity, and toxicity in normal or adrenalectomized mice.

Adjuvants, Immunologic↗

[New studies on inhibition of tRNA N2 guanine methyltransferase by S-adenosyl-homocysteine and S-adenosyl-methionine analogs].

New structural analogs of S-adenosyl homocysteine (SAH) 1-9, 11-14, 19-21) and of S-adenosyl methionine (15-18) have been tested as inhibitors of a N-2 guanine methyltransferase extract from rabbit liver with E. coli B tRNA as substrate. The sulfonium compounds (mixture of +/- diastereoisomers) are more inhibitory than the sulfide derivatives but less inhibitory than SAH itself. The replacement of the aminoacid chain in SAH by various alphatic radicals leads to a correlation between their bulk and the size of the enzymatic site. The monosubstitution of N-6 amino group does not affect significantly the inhibitory effect, which is completely canceled by the disubstitution of N-6.

Animals↗

Modulation of the immune response by a synthetic adjuvant and analogs.

N-Acetylmuramyl-L-alanyl-D-isoglutamine increases the humoral immune response of mice when given in aqueous media instead of the usual water-in-oil emulsions. Moreover, this compound is adjuvant active even by the oral route. In view of studying the relation between chemical structure and biological activity, several synthetic analogs were tested. The immune response could be modulated according to chemical modifications, and the synthetic analog with D- in place of L-alanine was shown to inhibit the immune response.

Adjuvants, Immunologic↗

Analysis of the cell wall of five strains of Myocbacterium tuberculosis BCG and of an attenuated human strain, W 115.

The chemical composition of the deproteinized, delipidated cell walls of five strains of BCG and of an attenuated human strain of Mycobacterium tuberculosis has been established, with special focus on their poly-L-glutamic acid content. All the cell walls have the same overall composition. Their poly-L-glutamic acid content varies from 0 to 4.6%. A correlation between the poly-L-glutamic acid content and the biological properties of the BCG strains reported in the literature could not be established.

Amino Acids↗

Presence and subcellular localization of two distinct mitogenic fractions in the cells of Nocardia rubra and Nocardia opaca: preparation of soluble mitogenic peptidoglycan fractions.

Fractionation of cells of Nocardia rubra and Nocardia opaca led to the separation of the cell wall and a "cytoplasmic" fraction. Both fractions were mitogenic for the splenocytes of AKR and nude mice and of rabbits. The peptidoglycan was the active part of the cell wall fraction. The products solubilized by the action of Streptomyces albus G peptidases on the peptidoglycan of N. rubra were mitogenic, but the products solubilized by lysoyme were not. Tentative structures are proposed for these fractions. The most active part of the cytoplasmic fractions could be sedimented by centrifugation and seemed to be related to the cytoplasmic membrane.

Animals↗

[Biological methylations in the crab Carcinus maenas; in vitro inhibition by a fraction purified from androgen gland extracts].

Extracts from muscles, testis, seminal vesicles and ovaries of the Crab, Carcinus maenas, have been studied in vitro, in presence of [14C]-methyl S-adenosylmethionine, with an E. coli tRNA as methyl acceptor. The highest level of methylases is found in the testis. It has been reported previously that a purified fraction extracted from the androgenic glands of Carcinus maenas inhibits the vitellogenesis in ovaries. We now show that the same fraction inhibits tRNA methylation in an extract of testis as methylase; a 50% inhibition is obtained with about 10 mug of a purified fraction corresponding to 15 glands. With an enzymatic preparation from the ovaries, a 50% inhibition of the tRNA methylase is observed with the purified extract from 4 glands.

Animals↗

[Isolation of a new keto-acid, produced from epsilon-N-trimethyllysine by Neurospora crassa].

A new epsilon-N-trimethyllysine metabolite has been isolated from the mycelium of Neurospora crassa. The labelled compound produced from incubations in vivo and in vitro from epsilon-N-trimethyl ([14-C]H3)L-lysine has been identified as 2-keto-epsilon-N-trimethyl-hexanoic acid by reducing its 2,4-dinitrophenyl hydrazone back to epsilon-N-trimethyllysine by hydrogenolysis in a Parr bomb. Analyses on TLC and in four different ion exchange chromatographic systems show the appearance of a ninhydrin positive product having the same Rf and the same retention time as epsilon-N-trimethyllysine; it contains more than 85% of the radioactivity of the 2,4-dinitrophenylhydrazone of the keto acid.

Chromatography, Ion Exchange↗

Transfer of the methyl group of methionine to choline and to tRNA in the honeybee Apis mellifica L.

Contrary to some previous reports on the absence of biological transmethylation reactions in some insect species, the transfer of the methyl group of methionine-methyl 14C leading to choline and to methylated bases in tRNA was shown in the honeybee Apis mellifica. The addition of antibiotics to the food of the insect does not diminish the incorporation of radioactivity, proving that intestinal bacteria are not responsible for the methylation reactions observed.

Animals↗

Enhancement of immunity against murine syngeneic tumors by a fraction extracted from non-pathogenic mycobacteria.

The data reported here demonstrate that a preparation extracted from nonpathogenic mycobacteria such as Mycobacterium smegmatis and hereafter referred to as interphase material protected mice against Ehrlich ascitic carcinoma, L-1210 leukemia, and another syngeneic lymphoid leukemia. Furthermore, mice treated by this preparation were much less susceptible to endotoxins than when stimulated by BCG (bacillus Calmette-Guerin) or M. smegmatis cells. Moreover, guinea pigs treated by interphase material administered in Freund's incomplete adjuvant showed an increased immune response, yet their sensitivity to tuberculin was much weaker than that of controls sensitized with Freund's complete adjuvant. Finally, resistance to Columbia SK virus infection could be demonstrated when interphase material was administered to mice prior to virus challenge.

Adjuvants, Immunologic↗