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Biomedical subjects

C Nauciel

Publications and source records attributed to C Nauciel.

At least 55 records · Page 3Linked to original sources

Impairment of lymphocyte proliferative responses and interleukin-2 production in susceptible (C57BL/6) mice infected with Salmonella typhimurium.

C57BL/6 (susceptible) and A/J (resistant) mice were infected intravenously with a temperature-sensitive mutant of Salmonella typhimurium. In C57BL/6 mice a marked depression of the proliferative response of spleen cells to B and T mitogens occurred and was maximal at 2-3 weeks post-infection, whereas only minor changes were found in A/J mice. This immunodepression was mediated, at least in part, by adherent cells. Moreover, spleen cells from infected C57BL/6 mice did not produce interleukin-2 (IL-2) after concanavalin A stimulation. The impairment of IL-2 production was not related to a defect in IL-1 release. The addition of IL-2 to spleen cells did not restore their ability to respond to mitogens. The depression of mitogenic responses in infected C57BL/6 mice occurred at a time when increased resistance was present.

Animals↗

[Enterobacter cloacae and E. aerogenes septicemia: emergence of resistant variants (derepressed cephalosporinase) during treatment with third-generation cephalosporins].

From three patients hospitalised in intensive care units with Enterobacter septicaemia (two cases with E. cloacae, and one with E. aerogenes), cefotaxime therapy, alone or in combination with an aminoglycoside, selected variants (R) with increased resistance to beta-lactam antibiotics. The cross-resistance extended to all the beta-lactam antibiotics tested, penicillins and cephalosporins, including third-generation cephalosporins. The crude extracts of uninduced cultures of R variants showed high beta-lactamase activity and of the cephalosporinase type. These variants were selected in vitro with a frequency of 10(-6) to 10(-7) and may result from a mutation involving the regulation of Enterobacter cephalosporinases, usually inducible. Data from the literature indicated that this new type of resistance is actually emerging and observed not only in Enterobacter sp. The problem of emergence of R variants exhibiting cross-resistance to beta-lactam antibiotics should be considered when third-generation cephalosporins are used.

Adult↗

Interleukin 1, a mediator of immunoadjuvant peptidoglycans.

Bacterial peptidoglycans and the synthetic analog muramyl dipeptide possess various immunomodulating properties (adjuvant effect, increase of resistance to infectious agents and to tumor growth). They are able to induce B cell activation and to stimulate macrophages to produce monokines such as Interleukin 1 (IL 1). IL 1 plays an essential role in immune response. It promotes thymocytes maturation and Interleukin 2 secretion by antigen sensitive T cells, which in turn triggers regulatory T cells. Moreover, it is involved in the proliferation and differentiation of B cells. There is a correlation between the immunoenhancing effect of PG of a definite structure and their ability to induce IL 1 secretion. Non-adjuvant PG were inactive. This suggests that one of the major mechanisms of action of adjuvant PG could be the stimulation of IL 1 synthesis.

Acetylmuramyl-Alanyl-Isoglutamine↗

Induction of interleukin 1 secretion by murine macrophages and human monocytes after stimulation by RU 41740, a bacterial immunomodulator.

RU 41740, a glycoprotein extract from K. pneumoniae K2O1 strain, is an immunomodulating compound which has been shown to reduce infectious episodes in patients prone to recurrent infections. Data from preliminary experiments suggest that RU 41740 may affect several target cells, including T cells, B cells or macrophages. In the present report we show that RU 41740 can trigger mouse macrophages and human adherent mononuclear cells to produce interleukin 1 activity. Indeed, supernatants from mouse peritoneal adherent cells and human monocytes incubated in presence of RU 41740, can stimulate blastogenesis in thymocytes from C3H/HeJ mice. The data suggest that the immunomodulating effect of RU 41740 could be related to its ability to induce interleukin 1 production.

Animals↗

Host response to infection with a temperature-sensitive mutant of Salmonella typhimurium in a susceptible and a resistant strain of mice.

The inoculation of a temperature-sensitive mutant of Salmonella typhimurium induced a long-lasting infection in susceptible (C57BL/6) and resistant (A/J) mice. During week 1 of infection, the number of bacteria in the spleens was similar in both mouse strains. Then, the decrease of bacteria was more rapid in the resistant strain. Splenomegaly and granulomatous hepatitis were more severe in the susceptible strain. The immune response induced by this infection was studied. In both mouse strains delayed-type hypersensitivity to Salmonella antigens was present, and resistance to reinfection with a virulent strain of S. typhimurium or with Listeria monocytogenes appeared with the same kinetics. Thus, it does not seem that the gene(s) controlling natural resistance to S. typhimurium act(s) on acquired immunity.

Animals↗

[Aeromonas hydrophila septicemia: 3 cases, 1 with mediastinitis].

Three cases of Aeromonas hydrophila septicaemia are reported. The first case concerned a 51 years old patient suffering from drowning who had previously been in good health and who died after a few days of refractory hypoxaemia. The second case was an 8 years old child with trisomy 21 operated for a congenital cardiac defect. The portal of entry was a catheter and the septicaemia was complicated by A. hydrophila mediastinitis, a complication which has not been described previously. The third case was a 75 years old man with no previous medical history, whose hobby was gardening. He developed septicaemia after a flu-like illness. A. hydrophila is a mobile Gram negative bacillus whose natural habitat is water. It appears to be an exceptional and temporary contaminant of the human G I tract. Clinical infection is rare and usually focal: gastroenteritis, infection of soft tissues after trauma in aquatic surroundings. In 60 out of 82 cases there was a documented deficiency in the patient's immune defenses. A digestive portal of entry was suspected in 63 cases but only rarely proved. In one of our cases the portal of entry was septic thrombophlebitis induced by an indwelling catheter; this complication has not previously been reported. The clinical picture of A. hydrophila septicaemia is characterised by the relative high incidence of Echtyma gangrenosum. The lethal outcome in 50 p. 100 of cases is often related to the patient's general condition. The sensitivity of the three cultures isolated was tested against third generation cephalosporins: they were effective in each occasion.

Aeromonas↗

Induction of interleukin 1 secretion by adjuvant-active peptidoglycans.

The ability of differently structured, purified peptidoglycans (PG) to induce interleukin 1 (IL1) secretion was compared. PG from Bacillus megaterium and Staphylococcus aureus stimulated the production of IL1 by mouse peritoneal macrophages and human adherent mononuclear cells, whereas PG from Micrococcus lysodeikticus and Corynebacterium poinsettiae were inactive. There was a correlation between the ability of PG to induce IL1 secretion and previously demonstrated immunoenhancing activities (adjuvant effect, increase of resistance to tumor growth) of PG. PG solubilization by lysozyme decreased but did not abolish the PG effect on IL1 secretion. Active PG induced IL1 production in nude mice and in the C3H/HeJ strain (which is unresponsive to lipopolysaccharides).

Adjuvants, Immunologic↗

Cytotoxic responses induced by peptidoglycans with or without in vivo antitumor activity.

Cytotoxic responses mediated by effector cells stimulated in vivo were studied after ip injection in mice of peptidoglycans extracted from gram-positive bacteria. A comparison was done between Staphylococcus aureus peptidoglycan (PGS), which possessed an antitumor effect, and Micrococcus lysodeikticus peptidoglycan, which was ineffective against tumors. Both peptidoglycans induced similar effects on the modulation of T-cell cytotoxic response. Both were able to stimulate splenic and peritoneal nonspecific cytotoxicity against YAC-1 lymphoid tumor cells, but only PGS could induce cytotoxicity and cytostasis against solid tumor target cells.

Animals↗

Peptidoglycans extracted from gram-positive bacteria: expression of antitumor activity according to peptide structure and route of injection.

The antitumor effect of peptidoglycans of various structures extracted from different gram-positive bacteria was studied, on chemically induced fibrosarcomas, in C3H/He, C57BL/6, and (C57BL/6 X C3H/He)F1 mice. When given sc admixed with tumor cells, only some peptidoglycans (those extracted from Bacillus megaterium and Staphylococcus aureus) enhanced tumor resistance in syngeneic and semiallogeneic hosts, whereas other peptidoglycans (those extracted from Micrococcus lysodeikticus and Corynebacterium poinsettiae) possessed no antitumor effect. When tumor cells were given ip, administration of peptidoglycans by the same route was either without effect on tumor growth or it induced tumor enhancement. Enhancement could be observed with all of the peptidoglycans tested. The antitumor effect when given sc and the ability to stimulate the proliferation of B-lymphocytes were shared by the same two peptidoglycans, while the other two peptidoglycans were devoid of both activities. It appears that these biological activities depend on the structure of the peptide moiety of peptidoglycans and that mitogenic and antitumor responses are stimulated by similar structures.

Animals↗

Inhibition of tumor growth by the peptidoglycan from Bacillus megaterium.

When injected in admixture with tumor cells, the peptidoglycan extracted from Bacillus megaterium inhibited the growth of a chemically induced fibrosarcoma in syngeneic rats. In some instances, the tumor growth was totally suppressed. Animals rejecting mixed inocula exhibited a tumor-specific immunity. Peptidoglycan was not cytotoxic for tumor cells; it rendered macrophages nonspecifically cytotoxic.

Animals↗

Immunochemical study of the peptidoglycan of gram-negative bacteria.

The specificity of antibodies directed against the peptidoglycan of gram-negative bacteria was studied. The peptidoglycans of Proteus vulgaris, Escherichia coli, Moraxella glucidolytica, Neisseria perflava, give identical precipitin reactions. By means of inhibition studies with various peptidoglycan subunits and synthetic peptides, it was shown that the antibodies are essentially directed against the peptide moiety of the peptidoglycan: L-Ala-D-Glu (L)-mesoA2pm-(L)-D-Ala, that the peptide reacts better with antibodies when it is not cross-linked, and that the C-terminal portion-meso-A2pm-D-Ala of the peptide is immunodominant. These results explain the immunological identity of the peptidoglycans of gram-negative bacteria, which possess the same peptide subunit. Only weak cross-reactivity was observed with the peptidoglycans of gram-positive bacteria (Streptococcus faecium, Micrococcus lysodeikticus, Corynebacterium poinsettiae) where meso-diaminopimelic acid is replaced by L-lysine or L-homoserine. However, the peptidoglycan of Bacillus megaterium which possesses the same peptide subunit as gram-negative bacteria, gives only a reaction of partial identity with these bacteria. This result suggests the presence on the peptidoglycan of gram-negative bacteria, of other undefined antigenic determinants.

Bacteria↗

[Bacterial adjuvants in cell mediated immunity. Recent data].

Only some bacterial adjuvants are able to stimulate cell-mediated immunity. It has been shown recently that this property is due to a cell-wall component, the peptidoglycan. The relevance of these findings to tumor immunity has been discussed.

Adjuvants, Immunologic↗

Adjuvant activity of bacterial peptidoglycans.

Purified peptidoglycans isolated from various Gram negative and Gram positive bacteria can substitute for Mycobacteria in Freund's adjuvant. Monomeric subunits possess the same adjuvant activity. This activity seems to be related to the peptidic fraction.

Adjuvants, Immunologic↗

Mitogenic effect of bacterial peptidoglycans possessing adjuvant activity.

Two purified peptides extracted from E. coli or B. megaterium strongly stimulated the spleen lymphocytes of rabbits and of normal or nude mice. Both preparations can substitute for Mycobacteria in Freund's complete adjuvant. The peptidoglycan extracted from M. lysodeikticus by a similar procedure which lacks adjuvant activity, did not induce blast transformation. However, the monomere of the E. coli peptidoglycan was devoid of mitogenicity although it has also a marked adjuvant activity.

Adjuvants, Immunologic↗