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Biomedical subjects

P H Lagrange

Publications and source records attributed to P H Lagrange.

At least 55 records · Page 3Linked to original sources
PubMed1995

Immunological aspects of pulmonary tuberculosis in children.

In recent years new information has been collected about the immunological responses to pathogenic mycobacteria. More information on cellular and molecular responses of cells in murine and human tuberculosis has been produced and T cells' role in the production of selected cytokines has been clarified. Studies in mice have provided insight into the phases of the T cell response to virulent M. tuberculosis, the role of various T cell subsets, and the repertoire of antigens recognized by these cells. However, despite this new information, some of which has been confirmed in humans, large gaps remain in our knowledge about the immune response to this infection, particularly concerning cellular or molecular mechanisms involved in acquired protection. Even if some extrapolations from adult data can be made, large gaps in our knowledge exist on the potential immune defects in young infants who are prone to develop tuberculosis soon after infection.

Animals↗
PubMed1995

Analysis of the immunological humoral response to Mycobacterium tuberculosis glycolipid antigens (DAT, PGLTb1) for diagnosis of tuberculosis in HIV-seropositive and -seronegative patients.

Using an enzyme immunoassay (EIA) test, the concentrations of IgG antibodies against 2,3 diacyl trehalose (DAT) and phenolic glycolipid Tb1 (PGLTb1) were measured in the sera of 153 patients with active tuberculosis, 50 of whom were coinfected with HIV, and in the sera of 152 healthy blood donors, 149 asymptomatic HIV-seropositive patients, 12 HIV-seronegative patients with conditions simulating tuberculosis, 23 HIV-seropositive patients with disseminated infection caused by mycobacteria other than tuberculosis and 24 HIV-seropositive patients with pulmonary disease from whom mycobacteria was not isolated in culture. A slightly lower percentage (74%) of the HIV-seropositive than the HIV-seronegative (77%) tuberculosis patients were positive for anti-DAT and anti-PGLTb1 IgG antibodies, with a specificity ranging from 91 to 95%. There was no significant difference between EIA sensitivity in smear-positive and smear-negative patients with pulmonary tuberculosis for all HIV immune statuses and sites of disease (pulmonary vs. extrapulmonary). In HIV-seropositive patients, however, sensitivity was always lower for disseminated tuberculosis than for localized tuberculosis. Combining data for both the smear test and the EIA maximized sensitivity. The main value of the EIA test could be to provide early complementary information by antibody detection in patients with tuberculosis, particularly those with a negative smear test.

Adult↗
PubMed1995

Preliminary evaluation of a Mycobacterium tuberculosis lipooligosaccharide (LOS) antigen in the serological diagnosis of tuberculosis in HIV seropositive and seronegative patients.

OBJECTIVE: To assess the value of detection of specific IgG or IgM antibodies against three polar glycolipids of Mycobacterium tuberculosis in HIV seropositive and seronegative patients with documented active tuberculosis. DESIGN: Using an ELISA test, concentrations of IgM and IgG antibodies against phenolic glycolipid Tb1 (PGL Tb1), 2.3 diacyl trehalose (DAT) and polar lipooligosaccharide (LOS) were measured in the serum of 36 patients with active tuberculosis: 16 tuberculosis patients were coinfected with HIV (TB HIV+), and 20 were HIV seronegative (TB HIV-). 104 control sera were tested: they were collected from 50 healthy blood donors and from 54 asymptomatic HIV seropositive patients. Specificity, sensitivity and predictive positive and negative values were calculated. RESULTS: For the LOS antigen tested, sensitivity, specificity and predictive positive value of specific IgG antibodies were 75%, 95% and 84% respectively among the 36 tuberculosis patients. No significant results were obtained either with the IgM against the LOS antigen or with IgG against the DAT and PGL Tb1 antigens. Significant sensitivity and positive predictive values were demonstrated only with the ELISA test measuring specific IgG against the LOS antigen. The sensitivity was greater in the TB HIV+ subgroup (94%) as compared with the TB HIV- (60%) subgroup. These results were not related to different potential factors such as the site of disease (pulmonary or extrapulmonary) or by the acid-fast bacteria load as detected by the smear microscopic (Ziehl-Neelsen) examination. CONCLUSIONS: The results suggest that of the 3 antigens tested, only the LOS antigen is a potential marker for detecting the development of tuberculosis in HIV patients.

AIDS-Related Opportunistic Infections↗
PubMed1995

Point mutation in the pribnow box, the molecular basis of beta-lactamase overproduction in Klebsiella oxytoca.

Klebsiella oxytoca mutants resistant to a variety of beta-lactams were obtained in vitro on aztreonam. Constitutive beta-lactamase production was much higher in the mutants than in the susceptible strains (75-fold). The only difference observed in these mutants compared with the susceptible strains were point mutations in the Pribnow box: a transversion (G-->T) in the first base for one mutant or a transition (G-->A) in the fifth base of the -10 consensus sequence for the other three mutants. The transcriptional output of the beta-lactamase gene (blaOXY) from the mutants was significantly higher than that of the blaOXY gene from the susceptible strains.

Anti-Bacterial Agents↗
PubMed1995

[A very current aspect of the fate of infectious diseases: tuberculosis, leprosy and opportunistic mycobacteria].

The human mycobacterial diseases, such as tuberculosis and leprosy, are chronic infectious diseases and have been present for a long period of time with human beings. Clearly tuberculosis and leprosy have been on the wane long before effective therapy was introduced, each of them having a natural epidemic evolution, with onset, peak and decline. Such decline was apparently accelerating in recent decades, due to individual and collective measures aiming at controlling the diseases, and it gives the hope of their possible elimination in the early XXIe century. If for leprosy recent data seems to indicate a realistic hope, such one has been destroyed for tuberculosis, since worldwide reemergence of cases occurs, which was associated with non application of control measures and occurrence of the HIV infection. Such coinfection leads to immunodeficiency that increases the risk of tuberculosis and the development of disseminated opportunistic mycobacterioses, mostly due to M. avium. An increased persevering action in the control measures and the development of new ways of research on mycobacterial infections are even more necessary if one will master such devastating plaques.

Forecasting↗
PubMed1995

Mycobacterial polar glycopeptidolipids enhance resistance to experimental murine candidiasis.

Intraperitoneal administration of polar glycopeptidolipids extracted from Mycobacterium chelonae (pGPL-Mc) greatly increased the resistance of mice against a lethal disseminated Candida albicans infection. This enhanced resistance was demonstrated by an increase in the number of survivors and the prolongation of the mean survival time of animals following a lethal challenge. These effects were dependent upon the infective dose of Candida albicans, the dose of pGPL-Mc and the timing of its administration. This enhanced resistance was correlated with the development and persistence of a hyperleukocytosis, associated with a long lasting increase in the number of polymorphonuclear neutrophils. On the contrary, no candidacidal effect of the serum collected from pretreated mice was observed; suggesting that the ability of pGPL-Mc to increase resistance against Candida albicans infection is likely to be mediated by polymorphonuclear neutrophils. These results confirm previously described immunostimulating properties of pGPL-Mc and open the way for the evaluation of its effect in the prevention of opportunistic infections in neutropenic patients.

Adjuvants, Immunologic↗
PubMed1995

[Azithromycin, pharmacodynamic evaluation in animal models].

Several experimental models have been used in order to evaluate the in vivo efficacy of azithromycin against numerous human pathogenic bacteria and parasites, including comparison between azithromycin and other antibiotics belonging or not to the macrolide family. Using the experimental models, three major objectives can be distinguished: the comparative studies of the efficacy dose 50 (ED50) of azithromycin compared to other orally given antibiotics, the azithromycin efficacy in animal infected with intracellular multiplying micro-organisms, and the demonstration of the specific azithromycin accumulation in tissues in direct relationship with the local recruitment of phagocytic cells at the infectious foci. The ED50 of azithromycin has been compared with those of erythromycin or cefaclor in varying acute murine infections. Evidence was given of a similar efficacy for the three tested antibiotics. Nevertheless a marked advantage for azithromycin was observed in experimental local infections and with infections due to Gram-negative bacteria (Haemophilus influenzae, Branhamella catarrhalis). The second objective was to confirm in vivo the preferential efficacy of azithromycin in models using intracellular multiplying microorganisms, due to its great capacity to accumulate inside of professional phagocytes. Several models have been used, such as those performed with Listeria monocytogenes, Legionella pneumophila, S. typhimurium, Brucella melitensis, M. avium and C. trachomatis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

New World tegumentar leishmaniasis: chemotherapeutic activity of rifampicin in humans and experimental murine model.

Daily doses of 0.5 mg of rifampicin given intraperitoneally to mice after a challenge dose of 104 amastigotes of L. amazonensis led to a significant reduction of the size of local lesions. On the other hand, daily doses of 20 mg/kg to children or 1200 mg to adult patients infected with L. braziliensis did not bring any sign of improvement after 30 days of treatment. Our results formally contradict rifampicin as an alternative drug in Leishmania braziliensis infections.

Adolescent↗
PubMed1994

Klebsiella oxytoca: resistance to aztreonam by overproduction of the chromosomally encoded beta-lactamase.

Aztreonam-resistant Klebsiella oxytoca strain SL7811 was selected on agar containing 1 microgram of aztreonam per ml from a susceptible strain SL781. The MICs for the resistant mutant towards penicillins, aztreonam and ceftriaxone were much higher, to cefotaxime slightly higher and to ceftazidime unchanged. Synthesis of beta-lactamase was 223-fold greater in the mutant compared with the susceptible strain. SL781 and its resistant mutant SL7811 produced beta-lactamase with the same isoelectric point and substrate profile. The beta-lactamase genes from SL781 and SL7811 were cloned in plasmid pBGS18 giving pBOF-1 and pBOF-4 respectively. The sequences of the two putative promoters indicated two modifications in the resistant plasmid pBOF-4: a transversion (G-->T) in the first base of the -10 consensus sequence and a deletion of one C residue four base pairs upstream of the -10 hexamer.

Amino Acid Sequence↗
PubMed1994

Origin and impact of plasmid-mediated extended-spectrum beta-lactamases.

Resistance to oxyimino cephalosporins was originally highlighted by the emergence of plasmid-encoded extended-spectrum beta-lactamases deriving by mutation from TEM-1, TEM-2 and SHV type enzymes (class A). The broader spectrum of resistance produced by these enzymes is related to more amino acid substitutions, but susceptibility to seven alpha-methoxyimino cephalosporins and carbapenems was preserved until recently. Clavulanate-sensitive extended-spectrum beta-lactamases are distributed worldwide, mainly among Klebsiella pneumoniae isolates. Novel clavulanate-sensitive extended-spectrum beta-lactamases deriving from other class A enzymes (e.g. MEN-1 from beta la OXY, OXA-11 in Pseudomonas aeruginosa from PSE-2) have been reported. Recently, clavulanate-resistant extended-spectrum beta-lactamases (class C) were encountered amongst single isolates, mostly Klebsiella pneumoniae. These cephalosporinases or cefamycinases (usually chromosomally mediated) have expanded the spectrum of plasmid-encoded resistance to include seven alpha-methoxyimino cephalosporins. Thus far, only two isolates (1 Pseudomonas aeruginosa, 1 Bacteroides fragilis), both recovered in Japan, with plasmid-mediated resistance to carbapenems have been found.

Clavulanic Acids↗
PubMed1994

Synergic inhibitory activity of amphotericin-B and gamma interferon against intracellular Cryptococcus neoformans in murine macrophages.

Cryptococcus neoformans is responsible for pulmonary and meningal infections in HIV patients. The lack of effective cellular cooperation caused by the low level of CD4+ cells, and the resistance of C. neoformans to phagocytosis allows growth and persistence of the yeast in the host. We describe here an in-vitro model of intracellular replication of C. neoformans inside J774-A.1 macrophages, and the determination of the intracellular antifungal activity of amphotericin B and fluconazole alone or in association with IFN-gamma. The maximum inhibitory effect was observed with one MIC of amphotericin B and 100 or 1000 IU/mL of IFN-gamma. amphotericin B alone (at 1 x MIC), or either 1 x or 50 x MIC of fluconazole in normal or IFN-gamma activated macrophages, did not eradicate the ingested yeast. A potential underlying mechanism of the synergy of amphotericin B in IFN-gamma primed macrophages was investigated by measurement of nitrite level and by use of the NO synthase competitive inhibitor, NG-monomethyl L-arginine (NMMA). One MIC of amphotericin B was able to activate the synthesis of nitrogen reactive intermediates in IFN gamma-primed macrophages. NMMA treated infected macrophages responded less well to IFN-gamma priming, resulting in a moderate inhibition in subsequent amphotericin B exposure.

Amphotericin B↗
PubMed1994

Molecular epidemiology of Klebsiella pneumoniae strains that produce SHV-4 beta-lactamase and which were isolated in 14 French hospitals.

Preliminary results suggested that the diffusion in France of the SHV-4 extended-spectrum beta-lactamase was probably due to the spread of one single epidemic strain of Klebsiella pneumoniae. In this study, we tested various phenotypic and genotypic markers to compare K. pneumoniae strains producing this enzyme isolated in 14 French hospitals between 1987 and 1989. All of the strains were of the same capsule serotype, K25. Twelve of them were of the same biotype: weak urease activity and no sucrose fermentation. Among the six plasmid profiles observed, one accounted for eight strains. Large plasmids of 170 kb encoding SHV-4 beta-lactamase were present in all strains of K. pneumoniae and could be transferred by conjugation with high frequency to Escherichia coli J53-2 or HB101 from all except one strain. Plasmid EcoRI restriction patterns suggested that these plasmids were closely related and similar to pUD18 encoding SHV-3 beta-lactamase, originally described in France and differing from SHV-4 by one amino acid substitution. Ribotyping with EcoRI and HindIII and genomic fingerprinting with XbaI by pulsed-field gel electrophoresis were concordant and suggested that 12 of the isolates recovered from the 14 hospitals were probably the same strain. Dissemination in France of the SHV-4 extended-spectrum beta-lactamase was thus essentially due to the diffusion of a single K. pneumoniae clone.

Conjugation, Genetic↗
PubMed1994

Enhanced resistance against lethal disseminated Candida albicans infection in mice treated with polar glycopeptidolipids from Mycobacterium chelonae (pGPL-Mc).

Intraperitoneal administration of polar glycopeptidolipids extracted from Mycobacterium chelonae (pGPL-Mc) greatly increased the resistance of mice against a lethal disseminated Candida albicans infection. This enhanced resistance was demonstrated by an increase in the number of survivors and the prolongation of the mean survival time of animals following a lethal challenge. These effects were dependent upon the infective dose of Candida albicans, the dose of pGPL-Mc and the timing of its administration. This enhanced resistance was correlated with the development and persistence of a hyperleukocytosis, associated with a long lasting increase in the number of polymorphonuclear neutrophils. On the contrary, no candidacidal effect of the serum collected from pretreated mice was observed; suggesting that the ability of pGPL-Mc to increase resistance against Candida albicans infection is likely to be mediated by polymorphonuclear neutrophils. These results confirm previously described immunostimulating properties of pGPL-Mc and open the way for the evaluation of its effect in the prevention of opportunistic infections in neutropenic patients.

Adjuvants, Immunologic↗
PubMed1994

Trypanosoma cruzi: histopathology of endocrine system in immunocompromised mice.

Naturally immunocompromised athymic mice, neonatal mice and adult outbred OFI mice treated with the immunosuppressive agents cyclophosphamide (CY), dexamethasone (DM) and indomethacin (IM) were infected with trypomastigotes of Trypanosoma cruzi Y and CL strains. 10(4) parasites were used, except in the case of IM treatment, where mice received 10(3) trypomastigotes in one group and 10(5) in another. The course of parasitaemia, tissue distribution of amastigotes and time of mortality were compared with an infected thymus intact control group. Neonate and indomethacin treated mice presented the same pattern of parasitaemia. Death occurred as early as 9-10 days after infection. A single dose of CY 200 mg/kg given 5 days after infection enhanced the parasitaemia and increased the number of parasites in the tissues. All groups were similar in terms of colonization of the endocrine system by parasites and the adrenals showed the highest density of amastigotes nests. The thyroid gland (analysed only in neonates) showed intense amastigote accumulation. Colonization of the ovary was observed with amastigotes in both the theca interna and in the stroma. The testes (also examined only in the neonate) showed that the interstitial cells, the tunica albuginea of the seminiferous tubules and the loose connective tissue were infected. Athymic nude mice showed the most intense parasite colonization of the islets of Langerhans.

Adrenal Glands↗
PubMed1994

Protective effect of BCG against leprosy and its subtypes: a case-control study in southern Vietnam.

A case-control study was conducted to assess the protective effect of intradermal BCG against leprosy and its subtypes in southern Vietnam. A total of 177 cases were selected with a distribution by subtypes as follows: 38 TT, 23 BT, 51 BB, 36 BL, 22 LL, and 7 indeterminate. Two controls were matched with a case for age, sex, ethnic group, socioeconomic status, and district area. The odds ratio assessing the protective effect of BCG varied from 0.44 (0.19-1.03) in the BB subtype to 3.00 (0.24-37.5) in indeterminate leprosy; whereas its overall value was 0.71 (0.45-1.10) for leprosy per se. When all borderline leprosy types were pooled, the protective effect of BCG was found significant with an odds ratio of 0.48 (0.27-0.84). In the polar forms of leprosy, TT and LL, the odds ratio was > 1 with large confidence intervals. It is possible that BCG induces a shift in the immune response to a higher level of cell-mediated immunity. When BCG vaccination is given after primary infection with Mycobacterium leprae, this shift could be the cause of an increase in the risk of the occurrence of milder and transient forms of the disease. In TT forms BCG might reinforce the preexisting subclinical immunopathological reactions, and in stable LL forms BCG might be unable to induce any protective form of immunity. These results confirm the important variability in the protection offered by BCG with respect to the different types of leprosy, and may have important implications for the design and the interpretation of vaccine trials that should take into account the respective proportions of leprosy forms observed in the study region.

Adolescent↗
PubMed1994

[New information on the structure of mycobacteria].

Recent progress about the mycobacterial structures have been realized and two major structures have been concerned: the genome and the cell wall. From these acquired new knowledge several lines of clinical research and diagnosis application emerged. Cloning and sequencing of several mycobacterial genes led to the development of diagnostic tools (DNA probes, PCR, finger printings of indated mycobacterial strains) and the potential detection of multiding resistant strains of M. tuberculosis. Genetic manipulations involving various mycobacterial genes do open the way for more precise molecular approaches concerning virulence factors involved in the pathophysiological understanding of mycobacterial diseases. Comparative physico-chemical and ultra-structural analysis of the mycobacterial cell wall evoked a highly complexed cell wall structure, constituted of a double lipidic layer linked to the peptidoglycan (PG). The first layer is constituted of mycolic acids that are linked to the PG by arabinogalactan, and to the superficial layer by hydrophobic interactions of glycolipids. The superficial layer is constituted of amphiphatic glycolipids, having a lipidic banal pole and a polysaccharidic apical pole. The knowledge of the mycobacterial cell wall structure opened the way of: the development of immunological diagnostic tools, being now days in clinical evaluation phase, a better approach for host-bacteria relationship study at the cellular level (macrophage, lymphocytes), and the understanding of the mode of action of antimycobacterial drugs such as isoniazid and ethambutol.

Animals↗