Biomedical subjects

M Guenounou

Publications and source records attributed to M Guenounou.

At least 55 records · Page 3Linked to original sources

PubMed1991

[Detection of extended broad-spectrum beta-lactamases with the ATB MIC system].

The Enterobacteriaceae producing extended broad-spectrum beta-lactamases (ESB) must be detected even when their MIC to oxyiminocephalosporins are low. We tested 164 isolates (133 ESB, 31 non ESB) on two experimental ATB MIC plates containing cefotaxime or ceftazidime (0.06-128 mg/l) alone or associated with sulbactam (4 mg/l). Fifty four per cent of the ESB isolates are sensitive to cefotaxime, and 30% to ceftazidime. Respectively 95% and 94% of these bacteria have a synergism index (MIC CIII alone/MIC CIIII + sulbactam) greater than or equal to 4 with cefotaxime and ceftazidime. The isolates that do not produce ESB have all a rate less than 4. The ATB system can detect the extended broad spectrum beta-lactamases when low concentrations of cephalosporins are used, alone and in association with an inhibitor of beta-lactamases.

Cefotaxime↗

PubMed1990

Production of interleukin 1 and tumour necrosis factor activities in bronchoalveolar washings following infection of mice by influenza virus.

Mice were infected with influenza A virus by aerosol. Bronchoalveolar washings obtained from infected mice contained interleukin 1 (IL-1) and tumour necrosis factor (TNF) activities. IL-1 was present at day 4 post-infection but not at day 7. TNF activity was present at day 4 and day 7 post-infection. The presence of both these monokines was coincident with increased cell populations in the lungs. In vitro studies demonstrated that macrophages from non-infected mice produce IL-1 and TNF activities in response to live influenza A virus stimulation. These results suggest that a direct interaction between virus and alveolar macrophages leads to IL-1 and TNF production during the course of infection and could account for both the immune responses and the pathology that occur during influenza A virus infection.

Animals↗

PubMed1990

Murine monoclonal antibodies to Klebsiella pneumoniae protect against lethal endotoxemia and experimental infection with capsulated K. pneumoniae.

To prepare monoclonal antibodies (MAbs) directed against the core-lipid A fractions of smooth lipopoly-saccharide (LPS) from Klebsiella pneumoniae O1:K2, we immunized BALB/c mice with the LPS-associated proteins plus LPS. This preparation exposed the core-lipid A moiety, which is normally hidden in the micellar structure of classical LPS preparations. Among 10 MAbs selected for their reactivity with LPS-associated proteins plus LPS from K. pneumoniae O1:K2, 6 (3A3, 3C2, 3C4, 7D2, 11C3, and 12B6) were directed against the core fraction and 2 (6C5 and 10A5) were directed against the lipid A fraction. Only one (2A4) recognized the O antigen, and one (6D5) had an undefined specificity. When injected before challenge with K. pneumoniae O1:K2 LPS in galactosamine-sensitized mice, five of the MAbs (3C4, 6D5, 7D2, 11C3, and 12B6) provided protection in this model of lethal endotoxemia. MAb 7D2 was also protective in an experimental infection with capsulated K. pneumoniae O1:K2.

Animals↗

PubMed1990

[In vitro activity of 4 fluoroquinolones against Klebsiella pneumoniae. Distribution according to phenotype resistance to aminoglycosides or beta-lactams].

Minimal inhibitory concentrations (MIC) of pefloxacin (PEF), norfloxacin (NOR), ofloxacin (OFL) and ciprofloxacin (CIP) are evaluated by agar dilution against 100 Klebsiella pneumoniae strains isolated in hospital. MIC 50 and 90%, micrograms/ml, are respectively: CIP (0.25/8), OFL (1/16), NOR (1/32), PEF (2/64). We determined the phenotypes PEF/NOR/OFL/CIP by taking into account the critic concentrations of the French Committee for Antibiogram. The results are: SSSS = 45%, RI/RI/RI/RI = 20%, RI/SSS = 19%, RI/RI/RI/S = 8%, RI/RI/SS = 7%. When a strain is resistant to pefloxacin alone, the MICs of the other fluoroquinolones are higher than those of the sensitive strains. The resistance to fluoroquinolones is most frequent in strains that have acquired resistance to aminoglycosides or betalactams, but exists also in strains that have no acquired resistance to these antibiotics.

Aminoglycosides↗

PubMed1989

Suppression of primary antibody response in genetically susceptible mice infected with Salmonella typhimurium: restoration by catalase.

Susceptible C57BL/6 mice infected with a temperature-sensitive mutant of Salmonella typhimurium exhibited a marked depression of in vivo and in vitro primary antibody response to sheep erythrocytes which persisted for several weeks. The antibody response to a T-independent antigen (TNP-polyacrylamide) was also depressed. Cell-mixing experiments indicated that spleen cells from infected animals contained adherent suppressor cells and that the functional activity of T and B cells was unaffected. The antibody response of spleen cells from infected mice was restored by the addition of catalase, suggesting that hydrogen peroxide is involved in the mechanism of suppression.

Animals↗

PubMed1989

Immunological activities of RU-41740, a glycoprotein extract from Klebsiella pneumoniae. III. Role of LPS-like and LPS-non-related molecules.

RU-41740, a glycoprotein complex extracted from Klebsiella pneumoniae, is an immunomodulating agent which acts on B cells and macrophages. It has been shown that RU-41740 is composed mainly of two macromolecular fractions, F1, having an LPS-related structure, and P1, with a proteoglycan structure. In the present paper, the effects of these molecules on B cells and on IL-1 and tumour necrosis factor (TNF), production by macrophages were compared. Data reveal that both fractions were mitogenic for murine B cells and induced IL-1 and TNF production by macrophages. The LPS-like fraction (F1) was sensitive to polymyxin B and was unable to activate macrophages and spleen cells from LPS non-responder mice. The P1 fraction was mitogenic for B cells and induced the production of IL-1 and TNF activities by macrophages from LPS non-responder C3H/HeJ mice. The cytotoxic activity was due to TNF alpha, since treatment with anti-TNF alpha antiserum abrogated the lytic activity of supernatants from stimulated macrophages. The differences observed between P1 and F1 fractions in terms of sensitivity to polymyxin B and activity towards C3H/HeJ spleen cells and macrophages suggest that the two structurally distinct molecules isolated from RU-41740 could act at different sites on immunocompetent cells.

Adjuvants, Immunologic↗

PubMed1989

Protective effects of murine monoclonal antibodies in experimental septicemia: E. coli antibodies protect against different serotypes of E. coli.

Murine monoclonal antibodies that bind outer membrane antigens of the J5 mutant of Escherichia coli O111:B4 were derived from spleen cells of BALB/c mice immunized with killed whole cells and boosted with lipopolysaccharide (LPS) and LPS-associated proteins. Seven hybridomas were selected for their reactivity against the J5 LPS; they cross-reacted with O111, O55, O127, and O128 E. coli LPS. One (B7B3) also reacted with the Serratia marcescens LPS and Klebsiella pneumoniae lipid A. A protective effect was obtained with D6B4 antibody in a lethal endotoxemia model induced by LPS from O111, O127, and O128 E. coli serotypes in D-galactosamine-sensitized mice. D6B4 and D6B3 antibodies protected mice infected with E. coli O111:B4, when administered before infection. The D6B4 antibody was also protective when administered after infection. The antibodies D6B3 and D4B5 were protective in heterologous infection induced by E. coli O2:K1.

Animals↗

PubMed1989

[In vitro and in vivo activity of a combination of clavulanic acid and amoxicillin against Klebsiella pneumoniae producing extended broad-spectrum betalactamase (CTX-1, SHV-3, SHV-4)].

In vitro activity of an aminopenicillin (amoxicillin or ampicillin) combined with a betalactamase inhibitor (clavulanic acid or sulbactam, 2 mg/l) was examined against 39 strains of K. pneumoniae producing 3 types of extended broad spectrum betalactamases (CTX-1, SHV-3, SHV-4). Clavulanic acid produces the best synergistic effect. The in vivo activity of Augmentin (amoxicillin + clavulanic acid), 1 g once or twice a day, during 10 +/- 3 days was evaluated on 10 cases urinary tract infections in paraplegic patients. After 3 days, no leucocyturia was observed and bacteria were no more detected. The inhibitory effect of clavulanic acid for the extended broad-spectrum betalactamases shows that such an association could be probably chosen as well for treatment urinary infection.

Amoxicillin↗

PubMed1989

[Broad spectrum beta-lactamases and the API ATB 244 system: the need for detection].

API ATB 24H is an automated system designed to test the sensitivity of bacteria to antibiotics. Using this system we found that it was not fully able to detect acquired resistance to oxy-iminocephalosporins in enterobacteriaceae producing extended broad spectrum betalactamase (CTX-1, SHV-3, SHV-4). However, the frequency of detection varied with the type of API SYSTEM (ATB G-, ATB PSE), the nature of beta lactam antibiotic (cefotaxime, ceftazidime) and the type of beta lactamase produced. Considering the fact that this new mechanism of resistance must be taken into account, we suggest that the most simple method for the detection of oxy-imini beta lactamases is a double disk test of synergy between Augmentin (acid clavulanic + amoxycillin) and 1 disk of oxy-iminocephalosporin.

Cephalosporins↗

PubMed1988

[Current status of aminoglycoside resistance in hospital Enterobacteriaceae].

We studied the susceptibility of Enterobacteriaceae to four aminoglycosides (gentamicin, tobramycin, netilmicin et amikacin). We determined their phenotypes of resistance by taking into account both the critic concentrations of the CFA (french committee for antibiogram) and the MIC of the main susceptible population of each species. The most frequent phenotypes were GTNt, TNtA and GTNtA. Amikacin resistance including phenotypes were essentially found in Klebsiella and Serratia (35% and 53% of the strains, respectively); with respect to amikacin, the phenotype expression may be insufficient to exceed the sensitive critic concentration of the CFA. Amikacin resistant strains were isolated from chronically infected patients with devices, such as urinary catheters or tracheal cannula. These results suggest a strains or plasmids outbreak.

Amikacin↗

PubMed1987

Human alpha 1-acid glycoprotein-exposed macrophages release interleukin 1 inhibitory activity.

The concanavalin A-unreactive variants of alpha 1-acid glycoprotein introduced in culture medium of monocytes/macrophages induces the inhibition of thymocyte proliferative activity of interleukin 1. LPS or LPS receptors were not involved in the activity of alpha 1-acid glycoprotein on macrophages. alpha 1-acid glycoprotein did not show any direct effect on thymocytes whereas the monocyte/macrophage-supernatant inhibited the interleukin 1 proliferative effect. The activity of tumor necrosis factor and interleukin 2 was not altered by the alpha 1-acid glycoprotein-macrophage supernatant.

Animals↗

PubMed1987

Behavior of aldehyde moieties involved in the activation of suppressor cells by sodium periodate.

The treatment of mouse spleen cells with periodate at the optimal mitogenic concentration (1 mM) induces the activation of suppressor cells of the in vitro antibody response and leads to the formation of aldehydes on the carbohydrate termini of the surface sialoglycoconjugates. These aldehyde moieties are found on the C8 (N-AN 8) and the C7 (N-AN 7) derivatives of sialic acid. Immediate borohydride reduction prevents the activation of the suppressor cells. Data from this work show that borohydride reduction must be performed within the first 6 hr to prevent the generation of suppressor cells; 18 hr after the initial periodate oxidation, borohydride treatment did not reverse the in vitro suppressive activity of periodate-treated cells. The kinetics of the disappearance of aldehydes from the cell surface were studied by using [3H]borohydride labeling and chromatographic analysis of sialic acid derivatives. About 70 to 80% of the aldehyde moieties were found to be present 6 hr after periodate oxidation. After 18 hr, 50 to 70% of the aldehyde had disappeared from the lymphocyte membrane. Oxidized sialyl residues disappear completely after 60 hr of culture. This period corresponds to the de novo synthesis of sialic acid residues on the surface of periodate-activated cells. The two classes of oxidized sialyl-glycoconjugates were found to behave in different ways. In effect, our data showed that the aldehydes remaining at 18 hr are mainly located on the gangliosides, whereas the aldehyde moieties located on high m.w. glycoproteins disappear from the cell surface between 9 and 18 hr. This would suggest that the remaining aldehydes located on gangliosides are not directly involved in the expression of suppressive activity.

Aldehydes↗

PubMed1987

[Modulation by quinolones of the in vitro proliferative response of splenic cells of the mouse and IL 1 production].

Besides their antibacterial activity, antibiotics can modulate immune response. In this work, we studied the effects of 6 quinolones (nalidixic and pipemidic acid, pefloxacin, norfloxacin, ofloxacin, ciprofloxacin) on Con A or LPS induced mitogenic response in mice. Data presented here show that pefloxacin and ofloxacin enhanced Con A (1 microgram/ml) induced proliferative response when used at low concentrations (0.1 microgram/ml and 1 microgram/ml). In the same conditions LPS induced response was not modified. When used at high concentrations (greater than 25 micrograms/ml), inhibition of both LPS and Con A induced responses was observed. Con A induced response needs interaction between macrophages and T lymphocytes. So, we investigated whether quinolones could act on interleukin 1 (IL 1) production by macrophages. Our results showed that pefloxacin and ofloxacin, used at low concentrations, enhanced LPS induced IL 1 production by macrophages.

Animals↗

PubMed1986

Release of a cytotoxic factor by macrophages stimulated with adjuvant-active peptidoglycans.

Bacterial peptidoglycans (PG) possess various immunomodulating activities, including the ability to inhibit the growth of some experimental tumors. We report here that PG induce the release by mouse (DBA/2 and C3H/HeJ) peritoneal macrophages of a cytotoxic factor (CF) that is active on L-929 cells and a 3-methylcholanthrene-induced tumor cell line but inactive on normal fibroblasts. Only the adjuvant-active PG (extracted from Bacillus megaterium and Staphylococcus aureus) were good inducers of the CF, whereas the adjuvant inactive PG (extracted from Micrococcus lysodeikticus and Corynebacterium poinsettiae) exhibited only weak activity. The CF was released within 2 hours of contact with PG either in serum-free or serum-containing media. The CF was inhibited neither by serum nor by the protease inhibitors that have been tested. It was stable for 30 minutes at 56 degrees C but inactivated after being heated for 10 minutes at 80 degrees C. After gel filtration, a single peak of activity at 80-90 kilodaltons was found. Chromatofocusing showed that the isoelectric point of the CF was 4.8.

Adjuvants, Immunologic↗

PubMed1986

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↗

PubMed1985

[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↗

PubMed1985

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↗

PubMed1985

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↗