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Biomedical subjects

E Lederer

Publications and source records attributed to E Lederer.

At least 73 records · Page 4Linked to original sources
PubMed1979

Relationship between inhibition of protein methylase I and inhibition of Rous sarcoma virus-induced cell transformation.

A correlation was found between inhibition of protein methylase I and inhibition of virus-induced cell transformation by structural analogs of S-adenosylhomocysteine; all good inhibitors of this enzyme are also good inhibitors of Rous sarcoma virus-induced chicke embryo fibroblast transformation. The inhibitory effect of these analogs was similar on enzymes from normal and transformed cells; no significant variation of the inhibition constants was observed after purification of protein methylase I. From the kinetic constants obtained, a structure-activity relationship can be established for protein methylase I.

Animals↗
PubMed1978

Immunotherapy with an intralesionally administered synthetic cord factor analogue.

Injection of emulsified 6,6'-di-O-2-tetradecyl-3-hydroxyoctadecanoyl-a, a trehalose designated C76, a synthetic analogue of the mycobacterial glycolipid trehalose-6,6'-dimycolate (TDM), into transplants of an established, syngeneic murine fibrosarcoma induced complete regression of tumor in a number of animals. The number of animals in which tumor regressed completely dependent on the amount of oil in the emulsion. On a weight basis, C76 was at least as active as TDM. Intralesional injection of an emulsified mixture of C76 and endotoxin (ET) or of TDM and ET caused regression of an established transplant of a guinea-pig hepatoma in syngeneic animals. In mice, intravenously administered emulsions of C76 were less toxic and less granulomagenic than those made with TDM.

Animals↗
PubMed1978

Structure of iturine A, a peptidolipid antibiotic from Bacillus subtilis.

A mixture of iturines extracted from Bacillus subtilis gave, on column chromatography, iturine A, iturine B, and iturine C. Iturine A has the entire antifungal activity. It is a mixture of two homologous peptidolipids C48,H74N12O14 and C49H76N12O14 (mp 177 degrees C, [alpha]D-1.7 degrees in methanol (c 0.05 g/mL); mol wt 1042 and 1056). The lipid moiety is a mixture of 3-amino-12-methyltridecanoic acid and 3-amino-12-methyltetradecanoic acid. The peptide moiety contains 7 mol of amino acids: D-Asn2, L-Asn, L-Gln, L-Pro, L-Ser, and D-Tyr. A cyclic structure for iturine A with the serine residue linked to the fatty amino acids through a peptide bond has been domonstrated. By mild HCl hydrolysis, lipid-soluble and water-soluble peptides were obtained. They were analyzed by chemical methods and by mass spectrometry. Permethylated and perdeuteriomethylated derivatives of iturine A were also subjected to mass spectrometric analysis. Both chemical analysis and mass spectrometry led to the cyclic structure I for iturine A.

Amino Acid Sequence↗
PubMed1978

In vivo and in vitro stimulation of nonspecific immunity by the beta-D-p-aminophenyl glycoside of N-acetylmuramyl-L-alanyl-D-isoglutamine and an oligomer prepared by cross-linking with glutaraldehyde.

Several biological activities of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP for muramyl dipeptide), a synthetic immunoadjuvant, are inhibited after glycosidation with p-aminophenol. Thus, this glycoside does not induce an increase humoral antibody response in mice when injected in saline, although it retains its stimulatory effect on circulating antibodies and delayed hypersensitivity after administration in a water-in-oil emulsion. The capacity of MDP to stimulate mouse spleen cells is lost, and, moreover, the analogue is unable to increase nonspecific resistance to infection under conditions where MDP is active. After cross-linking of the beta-D-p-aminophenyl glycoside of MDP with glutaraldehyde, several biological activities of MDP are recovered. Moreover, the cross-linked oligomer (molecular weight, approximately 6,000 daltons) is able to stimulate the uptake of thymidine by spleen cells from a strain of mice weakly responsive to MDP and is more active than MDP in protecting mice against bacterial challenge.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1978

Inhibition of tRNA methylation in vitro and in whole cells by an oncostatic S-adenosyl-homocysteine (SAH) analogue: 5'-deoxy 5'-S-isobutyl adenosine (SIBA).

A high increase in the amount of methylated tRNA bases was found in vivo in Rous sarcoma virus infected and transformed chick embryo fibroblasts in comparison with normal cells, tRNA methylases extracted from transformed cells showed also higher activity in vitro with a heterologous substrate. 5'-deoxy-5'-S-isobutyl adenosine, (a structural analogue of S-adenosyl-L homocysteine), which inhibits virus-induced cell transformation, inhibits also the increase of incorporation of labelled methyl groups into tRNA in infected and transformed cells. When normal cells are grown in the presence of this inhibitor, undermethylated tRNAs are obtained. The effect of the drug is different in normal, infected and transformed cells. The methylation of the different bases is inhibited in vitro and in vivo to various extent. The effect of this substance on tRNA methylation may be the cause of its inhibitory effect on cell transformation.

Avian Sarcoma Viruses↗
PubMed1978

Induction of interferon synthesis in mice by fractions from Nocardia.

Three fractions of Nocardia, Nocardia water-soluble mitogen (NWSM), Nocardia water-soluble mitogen pellet (NWSMP), and the cell wall peptidoglycan, which are mitogenic for B lymphocytes, were able to induce circulating interferon in mice, NWSMP and NWSM being the most active. The peak of interferon appeared about 2 h after injection. The interferon induced by NSWMP and NWSM was acid stable and antigenically related to viral interferon, as shown by neutralization with antibodies directed against Newcastle disease virus-induced interferon.

Animals↗
PubMed1978

Kinetics of the humoral and cellular immune response of guinea pigs after injection of the synthetic adjuvant N-acetylmuramyl L-alanyl-D-isoglutamine: comparison with Freund complete adjuvant.

We studied the time course of humoral and cellular immunity of guinea pigs injected with the synthetic adjuvant N-acetylmuramyl L-alanyl-D-isoglutamine (MDP Pasteur, 10 microgram) in Freund incomplete adjuvant; the kinetics were compared with those obtained with Freund complete adjuvant (50 microgram of whole Mycobacterium butyricum). The antibody response to ovalbumin was faster and higher with MDP, but dropped sooner to a low level; the secondary response was, however, again higher for MDP than for Freund complete adjuvant. Cellular immunity, as measured by delayed hypersensitivity, and migration inhibition factor production werepositive for both adjuvants. The same response was followed in animals injected with MDPA, the nonamidated analog of MDP; the same kinetics as for Freund incomplete adjuvant were obtained for the primary response, but the secondary response was stronger and gave a positive delayed hypersensitivity reaction.

Adjuvants, Immunologic↗
PubMed1978

Nonspecific immunostimulant activities of synthetic trehalose-6,6'-diesters (lower homologs of cord factor).

Mycobacterial cord factors (6,6'-diesters of trehalose with mycolic acids ranging from C80 to C90) have been shown to protect mice effectively against infection with Klebsiella pneumoniae or with Listeria monocytogenes. Our present findings indicate that the low-molecular-weight cord factor of Corynebacterium diphtheriae (with corynomycolic acids ranging from C28 PTO C36) is equally active. Moreover, its synthetic analog (with synthetic C32 mycolic acid) has the same activity. Two lower synthetic 6,6'-diesters of trehalose with C22 acids, which are described here for the first time, as well as dipalmitate and a dioleate of sucrose, were found inactive. The synthetic C76 trehalose diesters, which are capable of enhancing nonspecific resistance to infection, increase the immune response in mice, even when injected in metabolizable oil. They induce in the injected paws an inflammatory process weaker and more transient than the natural cord factor.

Adjuvants, Immunologic↗
PubMed1977

[Inhibition of biological methylations by t,t-farnesylacetone, a constituant of the androgenic gland of the male crab, Carcinus maenas].

t, t-farnesylacetone 1 and hexahydrofarnesylacetone 2 have been previously identified in extracts from the androgenic gland of the male Crab Carcinus maenas. These compounds inhibit in vitro the methylation of E. coli B tRNA and of Calf thymus histones with S-adenosylmethionine methyl-14C as methyl donor and methylases from Crab testis. Rat liver or a 1-adenine methylase from a Mouse plasmocytoma (1 is approximately 200 times more active than 2).

Animals↗
PubMed1977

[Methylation of tRNA in Carcinus maenas gonadal cultures: inhibition by purified androgenic gland extract].

Subcultures of ovaries and testis of the crab Carcinus maenas have been performed in the presence of L-[Me-14C]methionine. Introduction in the medium of a chromatographically-purified liposoluble fraction from the androgenic glands of the same animal inhibits the biological methylation of the tRNA of the ovaries by 62%. The inhibition of methylation of five individual bases varies from 45% to 84%. No inhibition of tRNA methylation is observed under the same conditions with testis subcultures.

Animals↗