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M Parant

Publications and source records attributed to M Parant.

At least 55 records · Page 3Linked to original sources
PubMed1980

Antiviral response elicited by a completely synthetic antigen with built-in adjuvanticity.

In a previous study we demonstrated that antiviral response against the coliphage MS-2 can be elicited by immunization with a synthetic antigen consisting of a conjugate (P2-A -- L) of a synthetic fragment (P2) of the virus coat protein attached to a synthetic polymeric carrier. The antiviral response was induced when the antigen was administered in complete Freund's adjuvant or when it was administered in incomplete adjuvant, provided that a peptidoglycan was covalently attached to it. In the present study we demonstrate the adjuvant effect of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) in this system. Immunization with a mixture of MDP and P2-A -- L brought about only slight enhancement in the titer of neutralizing antibodies, as compared to the immunization with P2-A -- L in saline. The best results were achieved when the MDP was chemically conjugated to P2-A -- L. This completely synthetic material, when administered in aqueous solution, yielded highly inactivating antiserum with a titer similar to that obtained with complete Freund's adjuvant in the absence of MDP. MDP-P2-A -- L elicited also a humoral immune response to MDP, but with much lower titer than that induced by complete Freund's adjuvant containing P2-A -- L only. It was also observed that the capacity of MDP-P2-A -- L to increase resistance against infection was more than a 100-fold greater than that of unconjugated MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1980

Effect of indomethacin on increased resistance to bacterial infection and on febrile responses induced by muramyl dipeptide.

The pyrogenicity in the rabbit and the ability to stimulate nonspecific resistance to bacterial infection in the mouse of muramyl dipeptide (MDP), a synthetic immunoadjuvant, are known to be enhanced when the glycopeptide has been conjugated to a carrier. The effects of indomethacin on fever induced by MDP or its conjugated derivative were studied. Indomethacin reduced febrile responses to MDP or its derivative, although it did not decrease production of endogenous pyrogen in vivo or in vitro. When incubated with rabbit peritoneal cells, indomethacin suppressed the elevation in prostaglandin levels usually induced by MDP. When administered to mice, indomethacin alone stimulated resistance to bacterial infection and, under appropriate conditions, had a strong synergistic effect when combined with free or conjugated MDP. The results demonstrate that neither pyrogenicity nor increased prostaglandin levels are prerequisites for immunopotentiation by synthetic glycopeptides.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1980

Influence of indomethacin on various immunopharmacological effects of muramyl dipeptide (MDP).

Muramyl dipeptide (MDP) is a low molecular (less than 500 daltons) synthetic analogue of a streptococcal peptidoglycan subunit. It was demonstrated to be the minimal structure essential for eliciting the adjuvant effect ascribed to Freund's complete adjuvant (FCA). MDP was likewise shown to represent the minimal requirement for peptidoglycan-induced changes in temperature and it was at first concluded that there was an almost perfect correlation between pyrogenicity and adjuvant activity. However, other experiments showed that certain MDP derivatives were as adjuvant active without eliciting a febrile response in the rabbit. Moreover an anti-inflammatory substance such as indomethacin completely inhibits the pyrogenic effect of MDP but does not affect or even enhance various of its immunostimulant properties. Inhibition of MDP-induced fever is not associated with modification of leucopenia or production of circulating endogenous pyrogens observed after MDP injection. Indomethacin incubated with peritoneal macrophage cultures at a dose which blocks prostaglandin synthesis, does not decrease the production by MDP of endogenous pyrogens.

Acetylmuramyl-Alanyl-Isoglutamine↗
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

Enhancement of certain biological activities of muramyl dipeptide derivatives after conjugation to a multi-poly(DL-alanine)--poly(L-lysine) carrier.

N-Acetylmuramyl-L-Ala-D-Glu-NH2 (muramyl dipeptide) and several of its derivatives are effective immunoactivators that can enhance nonspecific resistance to infection but can also elicit fever. In contrast, one of its stereoisomers, N-acetylmuramyl-D-Ala-D-Glu-NH2, is devoid of both these activities. Our present report demonstrates that macromolecularization of muramyl dipeptide by attachment of several units to a multi-poly(DL-Ala)-poly(L-Lys) carrier potentiates both its pyrogenic and its immunostimulant activity. This branched polymer has been extensively used as carrier to various haptens. Surprisingly, inactive N-acetylmuramyl-D-Ala-D-Glu-NH2, after conjugation under the same conditions, becomes capable of increasing nonspecific immunity although its lack of pyrogenicity is not greatly modified. Moreover, the N-acetylmuramyl-D-Ala-D-Glu--NH2 conjugate remains devoid of adjuvant, sensitizing, or eliciting activity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

[Increase of non-specific resistance to infection by synthetic adjuvants].

MDP and some other synthetic glycopeptides which are endowed with adjuvant properties are also able to increase non-specific resistance of mice to bacterial infections. They are effective by various routes including the oral route, and this protective activity can be demonstrated in animals having a poor immune status.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1978

Enhancement of the neonate's nonspecific immunity to Klebsiella infection by muramyl dipeptide, a synthetic immunoadjuvant.

N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide) and certain derivatives that are structural analogs of part of the bacterial peptidoglycan monomer have been shown to be adjuvant active and to enhance the nonspecific immunity of adult mice infected by Klebsiella pneumoniae. In the present study muramyl dipeptide and two other synthetic analogs were found to be active in newborn mice. This activity could be demonstrated after administration by subcutaneous or even by oral route. In contrast to what was observed after treatment by lipopolysaccharide, 8-day-old mice were definitively protected against bacterial challenge by these glycopeptides. Therefore such molecules could have a great value in view of studying and correcting the neonate's unresponsiveness.

Adjuvants, Immunologic↗
PubMed1978

Prevention of endotoxin-induced abortion by treatment of mice with antisera.

Small amounts of bacterial lipopolysaccharides (LPS), usually extracted from smooth organisms, have previously been shown to interrupt pregnancy in mice. The findings reported here demonstrate that LPS obtained from rough bacterial strains were also abortifacient. Moreover, lipid A, which represents a common toxic structure of LPS in many species of gram-negative Enterobacteriaceae, had the same activity, whereas the nontoxic polysaccharide moiety did not affect pregnancy. Our data also showed that specific bacterial antisera raised in various animal species protected pregnant mice from the abortifacient effect of smooth or rough LPS, and that this activity disappeared after absorption of the antisera with homologous bacteria. Nevertheless, antibodies to lipid A protected pregnant female mice challenged with lipid A or even with LPS extracted from various organisms. Moreover, pregnant mice treated with both antiserum and an antiserotonin compound were protected more effectively against LPS-induced abortion than mice treated with either substance alone.

Abortion, Induced↗
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

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↗
PubMed1978

[Dermatosis caused by bone graft material (author's transl)].

Cases of dermatosis caused by surgical implants are not infrequently observed. They are represented by many clinical forms. The pathology slides most often reveal a more or less dense dermal infiltration associated with signs of allergic angeitis. The pathophysiology is described as an intermediate or retarded hypersensibility or continuous non-specific antigen stimulation. The diagnosis is confirmed by the cure following removal of the surgical implants since the epicutaneous tests are not always fiable. We noted two patients whose clinical profile ressembled that of hematodermie.

Adult↗
PubMed1977

[Increase in the non-specific resistance to infection in mice after oral administration of 2 synthetic glycopeptides with adjuvant activity].

Two synthetic glycopeptides (MurNAc-L-Ala-D-isoGln and MurNAc-L-Ala-D-Glu), having adjuvant activity, were shown to enhance non-specific resistance to infection against K. pneumoniae. These compounds were active by various routes including oral administration and even if administered after the challenge. Two steroisomers lacking adjuvant activity did not protect the infected Mice.

Adjuvants, Immunologic↗