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Biomedical subjects

E Lederer

Publications and source records attributed to E Lederer.

At least 55 records · Page 3Linked to original sources
PubMed1982

The effect of adenosine analogues on the in vitro growth of Trypanosoma cruzi.

Trypanosoma cruzi (Brazil strain) was maintained in liver infusion tryptose and medium supplemented with 5 or 10% foetal calf serum at 27 degrees C on a rotating shaker platform. 85 to 95% of the organisms under these conditions are epimastigotes and the medium supported logarithmic growth for up to 24 hours. The effect of S-isobutyl adenosine and Sinefungin against cultured T. cruzi epimastigotes was studied: growth rate was slowed by both in a dose-dependent fashion; 500 micrometer Sinefungin caused complete inhibition which was irreversible after 24-hour exposure but the effect of S-isobutyl adenosine (100 micrometer) was reversible. Motility and morphology appeared to be unaffected.

Adenosine↗
PubMed1982

Fate of two 14C labelled muramyl peptides: Ac-Mur-L-Ala-gamma-D-Glu-meso-A2pm and Ac-Mur-L-Ala-gamma-D-Glu-meso-A2pm-D-Ala-D-Ala in mice. Evaluation of their ability to increase non specific resistance to Klebsiella infection.

The metabolic fate in mice of two 14C labelled meso-A2pm containing muramyl-peptides, the muramyl-tripeptide (Ac-Mur-L-Ala-gamma-D-Glu-14C-meso-A2pm) (MTP) and the muramyl-pentapeptide (Ac-Mur-L-Ala-gamma-D-Glu-meso-A2pm-14C-D-Ala-14C-D-Ala) (MPP) has been studied. As with 14C-MDP, the radioactive muramyl-tripeptide and muramyl-pentapeptide disappear rapidly from the organs and the radioactivity is found mainly in the urine. In contrast to MDP, the two meso-A2pm containing muramyl-peptides are not excreted intact in the urine. In both cases labelled fragments have been identifed: meso-A2pm from MTP and the tetrapeptide gamma-D-Glu-meso-A2pm-D-Ala-D-Ala from MPP. The ability of the two muramyl-peptides to increase nonspecific resistance of mice to Klebsiella infection was also investigated. The muramyl-pentapeptide injected i.v. one day before a lethal dose of K. pneumoniae protects both adult and neonate mice, as does MDP itself; the muramyl-tripeptide is inactive.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Biological activity of a new synthetic muramyl peptide adjuvant devoid of pyrogenicity.

Immunostimulant activities of muramyl dipeptide (enhancement of specific immune responses and of nonspecific resistance to infection) were retained by its N-acetylmuramyl-L-alanyl-D-glutaminyl-n-butyl ester derivative, although very large amounts administered intravenously, or even by the very sensitive intracerebroventricular route, did not elicit fever in the rabbit. This analog also appeared to be devoid of other secondary effects which have been observed after administration of muramyl dipeptide.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1981

Immunotherapy of experimental cancer with a mixture of synthetic muramyl dipeptide and trehalose dimycolate.

The antitumor activity of a mixture of synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and trehalose-6,6'-dimycolate (TDM) (MDP+TDM) in emulsified form was studied in guinea pigs, each with a syngeneic dermal tumor and microscopically detectable metastases in regional lymph nodes. A single intralesional administration of an ultrasonically prepared emulsion containing MDP+TDM in squalane or in mineral oil caused tumor regression and elimination of lymph node metastases. Similar emulsions of MDP+TDM made with squalene or hexadecane were immunotherapeutically inactive.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1980

Stimulation of thymocyte mitogenic protein secretion and of cytostatic activity of mouse peritoneal macrophages by trehalose dimycolate and muramyldipeptide.

Immunomodulators of bacterial origin, such as muramyl-dipeptide (MDP) and trehalose dimycolate, are able to stimulate some important biological functions of macrophages, such as their capacity to secrete a monokine, the thymocyte mitogenic protein (TMP), and to limit the growth of mastocytoma cells in vitro. Adherent cells from the peritoneal cavity of untreated mice do not secrete significant amounts of TMP and are not cytostatic. In contrast, adherent peritoneal cells from mice injected with trehalose dimycolate (emulsified in water) secrete TMP and are strongly cytostatic for P815 cells. Trehalose dimycolate is also active when added in vitro: (a) it enhances the cytostatic action of thioglycollate-elicited macrophages; (b) alone or in sequence with MDP, it induces an appreciable cytostatic activity in resident macrophages; (c) it limits the decline of the strong cytostatic action of trehalose-dimycolate-elicited macrophages occurring during in vitro cultivation. MDP also stimulates the cytostatic activity of the macrophages in vitro. The most interesting effect of MDP is its capacity to induce a strong secretion of TMP after a short contact (1 h) with elicited macrophages.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1980

Induction of resistance to Schistosoma mansoni by natural cord factor and synthetic lower homologues.

Resistance to schistosomiasis in mice can be acquired either specifically, by primary infection with Schistosoma mansoni, or nonspecifically, by treatment with a variety of unrelated agents such as bacille Calmette-Guérin. Several immunoadjuvants related to mycobacteria were examined for their ability to induce resistance to schistosomiasis. Natural cord factor (6,6'-trehalose dimycolate), a 100-carbon synthetic cord factor analogue, and dipalmitate trehalose induced significant protection. Trehalose dibehenate and muramyl dipeptide did not induce consistent protection. Since protection acquired by primary schistosomal infection or by any of these potentiating agents is partial, their possible additive effect was evaluated. The resistance of mice with schistosomiasis that were injected with trehalose dipalmitate and challenged with schistosomal cercariae was increased, as assayed by recovery of schistosomula from the lungs and of adult worms from the portal system. Thus, these synthetic adjuvants not only induce partial protection against schistosomiasis, but also significantly enhance acquired immunity in mice with primary infections.

Adjuvants, Immunologic↗
PubMed1980

Immunostimulant activities of a lipophilic muramyl dipeptide derivative and of desmuramyl peptidolipid analogs.

The immunostimulant properties of a new muramyl dipeptide (MDP) derivative bearing a lipophilic moiety on the C-terminal end of the peptide chain are described. It is shown, in particular, that 1,O-(acetylmuramyl-L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate had increased immunostimulant activity in comparison with MDP. It induced hypersensitivity even when administered with an antigen in saline, and it gave higher protection against bacterial infections than did MDP. A quite unexpected finding was obtained with the corresponding desmuramyl compound 1,O-(L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate, which had no activity in producing humoral antibodies but was just as active as the muramic acid-containing compound in stimulating nonspecific resistance to bacterial infections. It was not pyrogenic. Modifications of the peptide moiety or the lipid moiety of this peptidolipid led to decrease, or even loss, of activity. These results show the importance of the N-acetylmuramyl moiety in MDP for humoral antibody production. The peptidolipid 1,O-(L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate is the first member of a new category of nonspecific immunostimulants.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Immunotherapy of an ascitic rat hepatoma with cord factor (trehalose-6, 6'-dimycolate) and synthetic analogues.

The ability of cord factor (trehalose-6, 6'-dimycolate) and a range of shorter carbon chain fatty acid trehalose diesters to suppress growth of an ascitic rat hepatoma has been examined and compared with that of whole, living BCG organisms. Aqueous suspensions of BCG, and cord factor in 0.4% arachis oil:Triton emulsion, injected intraperitoneally, retarded growth of up to 10(5) ascites tumour cells. Trehalose-6, 6'-dibehenate was also tumour-suppressive, but only against lower challenge inocula (10(4) cells). Trehalose-6, 6'-dipalmitate and 6,6'-di-0-2-tetradecyl -3-hydroxyoctadecanoyl alpha, alpha trehalose (designated C76) were virtually ineffective and 6,6' -di-0-2-eicosyl-3-hydroxy-tetracosanoyl alpha, alpha trehalose (designated C100) gave small and variable effects only against low challenge inocula. However, improved responses were seen with light mineral oil in place of arachis oil in the emulsions.

Animals↗
PubMed1979

[In vitro inhibition of tRNA methyltransferases by queen substance, a pheromone of queen honeybees].

The Queen Substance 1, a pheromone of the queen Honeybee Apis mellifica is an in vitro inhibitor of E. coli B tRNA methylations. This activity is not specific of the methylase source, as inhibitions have been observed with preparations from queen honeybee ovaries, Rat liver or a Mouse plasmocytoma 1-adenine methylase. These results, together with preceding ones concerning t, t-farnesyl-acetone 3, are discussed.

Animals↗
PubMed1979

Fate of the synthetic immunoadjuvant, muramyl dipeptide (14C-labelled) in the mouse.

Synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide or MDP) represents the smallest unit that can substitute for whole Mycobacteria in Freund's complete adjuvant. In this paper the fate of 14C-labelled (on the muramyl moiety) MDP is reported. Following intravenous or subcutaneous injection into mice, more than 50% of 14C-MDP was recovered in the urine after 30 min and more than 90% after 2 h. The labelled compound was found unchanged in the urine, as shown by detailed analyses. However, MDP was sequestered for a longer time at the site of injection when administered as a water-in-oil emulsion. Considering the relatively rapid elimination observed, it is suggested that the biological effects of MDP and related compounds, when administered in an aqueous medium, may be due to their activity at minute concentrations and/or an immediate action at the cellular level.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Synthesis of N-acetyl-muramyl-L-alanyl-D-glutamic-alpha-amide(MDP) or -alpha-methyl ester derivatives, bearing a lipophilic group at the C-terminal peptide end.

We report the synthesis of nine lipophilic derivatives of N-acetyl-muramyl-L-alanyl-D-glutamic-alpha-amide (MDP) or -alpha-methyl ester in which the gamma-carboxyl function of the D-glutamyl residue is either esterified by a medium chain alcohol or substituted by an L-alanyl residue esterified by a medium or long chain alcohol. A new method is described which easily allows one to obtain derivatives of MDP, bearing a free or substituted amino-acyl or peptidyl residue on the gamma-carboxyl function.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Regression of a murine fibrosarcoma after intralesional injection of a synthetic C39 glycolipid related to cord factor.

Intratumoral injection of ultrasonically prepared emulsions of the synthetic glycolipid methly 6-O-(2-tetradecyl-3-hydroxyoctadecanoyl)-alpha-D-glucopyranoside (designated C39) induced complete regression of transplants of a syngeneic murine fibrosarcoma in most of the treated animals as did 6,6'-di-O(2-tetradecyl-3-hydroxyoctadecanoyl)-alpha,alpha,-trehalose (designated C76) in a previous study. The C76 compound, about twice the molecular weight of C39, was more effective therapeutically than the smaller molecule. Ultrasonically prepared emulsions of C39 and C76 were not toxic when given intravenously. Intravenously administered emulsions of C39 prepared by mechanical grinding were more toxic, but less granulomagenic, than those containing C76. Squalane and squalene, but not peanut oil, were effective substitutes for mineral oil as carriers of C39 in the treatment of the tumor.

Animals↗