Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The modes of action of bis(tributyltin)oxide (TBTO) doses between 1 X 10(4) and 6 X 10(7) molecules per cell on a single environmental isolate of Legionella pneumophila were studied by monitoring the following parameters: (i) growth, (ii) cell viability, (iii) 14C-amino acid incorporation, (iv) 14CO2 production from 14C-amino acids, (v) [3H]uridine incorporation, (vi) [3H]thymidine incorporation, (vii) oxygen consumption, (viii) cellular ATP levels, and (ix) adenylate energy charge. The amount of TBTO associated with the cells in these laboratory cultures was also compared with that remaining in the suspending medium. Most of the TBTO (68 to 88%) was found to be associated with the cells. This result explained why the cellular responses which were measured did not correlate with the TBTO concentration, but rather with the dose of TBTO to which the cells were exposed. At the lower TBTO doses tested (10(4) to 10(7) molecules per cell) a log-normal relationship was observed between the reduction in growth rate and the TBTO concentration. At intermediate TBTO doses (ca. 10(7) molecules per cell) growth stasis occurred, with nearly 100% of the cells in these cultures remaining viable for at least 5 h after treatment. The cellular function which seemed to be primarily affected at these levels of TBTO was the energy conversion mechanism, since the decline in the rates of CO2 production, oxygen consumption, and macromolecular synthesis was preceded by an immediate (within 1 min) drop in the intracellular levels of ATP and the adenylate energy charge. At the higher TBTO doses greater than 10(7) molecules per cell) an initial, precipitous, drop in the number of viable cells was observed, which was followed by a further exponential reduction of viable cells in the treated culture. This dramatic increase in bactericidal activity with a slight increase in the TBTO dose indicated that the modes of bacteriostatic and bactericidal action of TBTO were different.
 ...
PMID:Bacteriostatic and bactericidal modes of action of bis(tributyltin)oxide on Legionella pneumophila. 618 98

Legionella pneumophila was susceptible to the antimicrobial action of oxygen metabolites generated by both the myeloperoxidase-H(2)O(2)-halide and the xanthine oxidase systems.
 ...
PMID:Effect of oxygen-dependent antimicrobial systems on Legionella pneumophila. 629 60

We examined 40 strains of Legionella for reduced-oxygen scavenging enzymes. Using a simple reaction chamber with a Swinney filter for the Beers and Sizer assay, we determined the catalase activity of live cells grown on buffered charcoal-yeast extract agar. For 29 strains of Legionella pneumophila, the apparent first-order rate constants for catalase ranged from 0.000 to 0.005. Similarly, low values ranging from 0.001 to 0.005 were observed for Legionella wadsworthii, Legionella oakridgensis, and Legionella gormanii. High catalase activities were found for Legionella jordanis, Legionella longbeachae, Legionella micdadei, and Legionella bozemanii, with first-order rate constant values of 0.010 to 0.035. Cell-free extracts were analyzed for catalase, peroxidase, and superoxide dismutase. Cell-free extracts of all strains had superoxide dismutase levels ranging from 8.2 to 30.5 U per mg of protein. The species could be characterized by their catalase and peroxidase since L. pneumophila and L. gormanii had only peroxidase (relative molecular weight [Mr], 150,000); L. dumoffii had a peroxidase (Mr, 150,000) plus a catalase (Mr, 174,000); and all remaining species had catalase only (Mr, 300,000, 220,000, or 150,000).
 ...
PMID:Determination of catalase, peroxidase, and superoxide dismutase within the genus Legionella. 649 Aug 28

Thioglycolate-elicited murine macrophages from genetically susceptible A/J mice activated with lipopolysaccharide (LPS) and infected with Legionella pneumophila in vitro evince marked inhibition of intracellular growth of this bacterium. The mechanism of inhibition by LPS-activated macrophages in terms of replication of this intracellular pathogen is unclear. LPS activation of murine macrophages induced a downshift in transferrin receptor (TfR) expression and reduction in cellular iron content, and this was correlated with augmented intracellular growth of Legionella in the cells. When LPS-stimulated macrophages were first saturated with iron, partial reversion of L. pneumophila growth restriction was observed. However, an excess of exogenous L-tryptophan (Trp) did not reverse this growth inhibition, nor did supplementation of the macrophage culture medium with both iron and Trp. The antilegionella activity of the macrophages induced by LPS activation was independent of reactive oxygen intermediates (ROI), since the scavengers catalase, superoxide dismutase, mannitol, and thiourea had no effect on growth restriction. Likewise, notwithstanding the ability of LPS-activated macrophages to synthesize reactive nitrogen intermediates (RNI), which was inhibited by L-arginine analogs NG-monomethyl-L-arginine and L-aminoguanidine), as well as by incubation in arginine-free medium, their ability to inhibit the intracellular replication of L. pneumophila was not affected. Thus, we conclude that LPS-activated macrophages inhibit the intracellular growth of L. pneumophila partially by iron-dependent, Trp-independent, and ROI- and RNI-independent mechanisms. We also suggest that additional unknown mechanisms are involved, since complete reversion was not obtained.
 ...
PMID:LPS inhibits the intracellular growth of Legionella pneumophila in thioglycolate elicited murine peritoneal macrophages by iron-dependent, tryptophan-independent, oxygen-independent, and arginine-independent mechanisms. 782 75

Legionella pneumophila, a facultative intracellular pathogen, replicates within and kills thioglycolate-elicited (TG) macrophages from A/J mice, while growth is inhibited in TG macrophages from BALB/c mice which show no impaired viability. The role of iron in BALB/c and A/J macrophages regarding their permissiveness to L. pneumophila intracellular growth was investigated. We previously reported that TG macrophages from the A/J mouse strain readily supported the intracellular growth of L. pneumophila, while resident macrophages from the same strain of mice were not permissive. Recently we also found that such a difference in permissiveness between both A/J macrophage populations may be explained, at least in part, to intracellular availability of iron. In this report, differences in permissiveness to L. pneumophila growth between A/J TG macrophages and BALB/c TG macrophages was not due to intracellular iron availability. BALB/c and A/J TG macrophages exhibited similar expression of transferrin receptor and cellular iron content. The treatment of BALB/c TG macrophages with different iron compounds, namely ferric nitrilotriacetate (12.5-100 microM), ferric citrate (12.5-100 microM) and transferrin (0.5-5 mg ml-1), did not stimulate the intracellular proliferation of L. pneumophila. The reduction of intracellular iron availability by treatment with antibodies against transferrin receptor or with desferrioxamine suppressed the growth of L. pneumophila within BALB/c TG macrophages, suggesting that these cells do not restrict L. pneumophila growth because of iron. The production of nitric oxide was also similar in both macrophage populations, as measured by the Griess reaction. However, the synthesis of oxygen reactive species was three times higher in non-permissive BALB/c macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Differences and similarities in permissive A/J versus non-permissive BALB/c murine macrophages infected with Legionella pneumophila: the role of iron. 792 Apr 66

To elucidate the role of the oxidative burst in macrophage resistance to Legionella infection, we examined a murine macrophage-like cell line, J774.1, for permissiveness to Legionella growth, using a mutant that has a selective defect in the oxidative burst after lipopolysaccharide (LPS) stimulation. Legionella pneumophila serogroup 1 was infected into J774.1 monolayers, and then the extent of bacterial growth was estimated by a CFU assay. Both the parental cell line, JA-4, and the LPS-resistant mutant, LPS1916, were permissive for Legionella growth but became nonpermissive after pretreatment with gamma interferon. However, pretreatment of LPS1916 cells with LPS failed to inhibit bacterial growth, although LPS-treated JA-4 cells exhibited inhibited multiplication of the bacteria. The bacterial growth inhibition in JA-4 and mutant LPS1916 cells was correlated with the extent of the oxidative burst in the cells, as judged by cytochrome c reduction but not nitrite production. Neither transferrin receptor expression nor the iron content in JA-4 and LPS1916 cells, with or without LPS treatment, was correlated with suppression of Legionella growth. These results suggest that the restriction of Legionella growth in J774.1 cells is due to a bactericidal effect of the oxidative burst rather than reduction of the iron supply to the intracellular bacteria and that the effectors are reactive oxygen intermediates and not reactive nitrogen intermediates.
 ...
PMID:Difference in Legionella pneumophila growth permissiveness between J774.1 murine macrophage-like JA-4 cells and lipopolysaccharide (LPS)-resistant mutant cells, LPS1916, after stimulation with LPS. 796 Jan 21

A/J mouse macrophages infected with Legionella pneumophila and treated with gamma interferon (IFN-gamma) in vitro developed potent antimicrobial activity. This antilegionella activity was independent of the macrophage capacity to generate reactive oxygen intermediates, since the oxygen radical scavengers catalase, superoxide dismutase, mannitol, and thiourea had no effect on the antilegionella activity of IFN-gamma-activated macrophages. Likewise, whereas the ability of IFN-gamma-activated macrophages to synthesize reactive nitrogen intermediates was markedly inhibited by the L-arginine (Arg) analogs, NG-monomethyl-L-arginine and L-aminoguanidine, as well as by incubation in L-Arg-free medium, their ability to inhibit the intracellular growth of L. pneumophila remained intact. The intracellular growth of L. pneumophila in A/J macrophages was inhibited by the iron(III) chelator desferrioxamine and reversed by Fe-transferrin as well as by ferric salts. Additionally, IFN-gamma-activated macrophages incorporated 28% less 59Fe(III) compared with nonactivated cells. Nonetheless, only partial blocking of growth restriction was observed when IFN-gamma-stimulated macrophages were saturated with iron(III). Indole-propionic acid, which appears to inhibit the biosynthesis of L-tryptophan (L-Trp), was an L-Trp-reversible growth inhibitor of L. pneumophila in macrophages, implying that the intracellular replication of this pathogen is also L-Trp dependent. However, an excess of exogenous L-Trp did not reverse the growth inhibition due to IFN-gamma, though a small synergistic effect was observed when the culture medium was supplemented with both iron(III) and L-Trp. We conclude that IFN-gamma-activated macrophages inhibit the intracellular proliferation of L. pneumophila by reactive oxygen intermediate- and reactive nitrogen intermediate-independent mechanisms and just partially by nutritionally dependent mechanisms. We also suggest that additional mechanisms, still unclear, may be involved, since complete reversion was never obtained and since at higher concentrations of IFN-gamma, iron(III) did not induce any significant reversion in the L. pneumophila growth inhibition.
 ...
PMID:Inhibition of Legionella pneumophila growth by gamma interferon in permissive A/J mouse macrophages: role of reactive oxygen species, nitric oxide, tryptophan, and iron(III). 803 89

A 72-year-old man was admitted to our hospital because of acute respiratory failure. Initially he had been diagnosed as having pneumonia in the lower left lung field and treated with cephem antibiotics by a local physician. Chest X-ray photograph revealed wide-spread infiltrates throughout both lungs, and chest CT scan revealed pleural effusions. The partial pressure of oxygen in arterial blood was 45.8 Torr. In the bronchoalveolar lavage fluid (BALF) specimen, legionella DNA was detected by the polymerase chain reaction (PCR) method. Thus, we were able to diagnose Legionella pneumonia immediately, and to treat the patient successfully.
 ...
PMID:[A patient with Legionella pneumonia diagnosed early by the PCR method]. 808 49

Previous reports have suggested that nosocomial and community Legionella pneumonia cases are similar. However, community and hospital characteristics, such as aquatic environment, antibiotic pressure (usage) and populations, are quite different, leading to the suspicion that Legionella infection may differ in the two settings. Univariate and multivariate analyses were performed to compare demographic data, risk factors, clinical, radiological and outcome data between 125 nosocomial and 33 community-acquired cases of Legionella pneumophila infection. Patients in the nosocomially acquired Legionella pneumonia (NALP) group were older than those in the community-acquired Legionella pneumonia (CALP) group. Univariate analysis showed that smoking habit, cough, thoracic pain, and extrapulmonary manifestations were more prevalent in the CALP group, whilst chronic lung disease and cancer were more prevalent in the NALP group. Moreover, patients in the NALP group were more likely to have received oxygen and corticosteroid therapy and also to have altered creatinine values than patients in the CALP group, whilst more patients in the latter group had altered alanine amino-transferase values. However, multivariate analysis failed to confirm most of these differences. Smoking habit and blood creatinine levels were the only variables remaining significant. In conclusion, demographic, clinical, laboratory, radiological and outcome data in nosocomial and community-acquired Legionella pneumonia are quite similar.
 ...
PMID:Nosocomial and community-acquired Legionella pneumonia: clinical comparative analysis. 862 Sep 64

The differentiation of HL-60, a human leukemic cell line, into monocyte-like cells (D3-HL-60 cells) is induced by 1,25-dihydroxyvitamin D3 (D3). We examined the effects of interferon (IFN) treatment of D3-HL-60 cells on the expression of cell surface antigens, the phagocytic activity for fluorescent beads, production of oxygen radicals, and intracellular growth of Legionella pneumophila. Activation of D3-HL-60 cells with IFN-gamma, Beta, and alpha for 24 h significantly increased expression of CD16, CD36, CD71, and HLA-DR antigens. IFN-gamma markedly enhanced the phagocytic activity of beads in D3-HL-60 cells. There was no significant difference in phagocytic activity between cells exposed to IFN-alpha or beta and untreated D3-HL-60 cells. IFN-alpha, beta, and gamma enhanced production of oxygen radicals, including superoxide, by D3-HL-60 cells. Superoxide production was enhanced to the greatest degree by IFN-gamma, followed by IFN-beta and then IFN-gamma. Intracellular growth of L. pneumophila in D3-HL-60 cells was inhibited by interferons (IFN-gamma > beta > gamma). Similar results were obtained in human mononuclear cells. These data indicate that interferons can act as biologic response modifiers not only in human mononuclear cells but also in differentiated leukemic cells. Our results may have implications for the development of differentiation therapy for treatment of leukemia.
 ...
PMID:Effects of interferon-alpha, beta, and gamma on the function of differentiated leukemic HL-60 cells induced by 1,25-dihydroxyvitamin D3. 872 74


<< Previous 1 2 3 4 5 6 7 8 Next >>