Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intraperitoneal administration of polar glycopeptidolipids extracted from Mycobacterium chelonae (GPLp-Mc) has led to reversal of Doxorubicin-induced leucopenia in a manner comparable to that effected by GM-CSF administered in a dose of 100 IU (2.5 micrograms/kg). The mode of action and the toxicity of this product are being studied. Results obtained on the mouse indicate that it would be worthwhile to undertake tests in man aimed at studying the effect of GPLp-Mc on chemotherapy- and radiotherapy-induced leukopenias, once toxicological studies have been carried out.
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PMID:[Activity of polar glycopeptidolipids from Mycobacterium chelonae in the reversal of chemically induced leukopenia in mice]. 142 16

Recombinant granulocyte/macrophage-colony-stimulating factor (rGM-CSF), prepared from Chinese hamster ovary (CHO) cells and Escherichia coli, was administered to 35 patients with the borderline and polar lepromatous forms of leprosy by the intradermal and subcutaneous routes at doses of 7.5-45.0 micrograms/d for 10 d. With each of these doses and routes, increases in the number of circulating eosinophils were noted. After the intradermal injection, the local skin sites demonstrated zones of roughening and micronodularity that appeared within 24-48 h and persisted for more than 6 d. Reinjection of sites led to enhanced areas of epidermal reaction. GM-CSF prepared from CHO cells was a more potent inducer of this effect. GM-CSF given by the subcutaneous route, at higher doses, failed to initiate these changes. At the microscopic level, the epidermis became thickened (+75%) with increased numbers and layers of enlarged keratinocytes. These contained increased numbers of ribosomes and prominent nucleoli, and were imbedded in a looser meshwork of the zona Pellucida. The modified keratinocytes remained MHC class II antigen negative throughout the course of the response. A major change in the dermis was the progressive accumulation of CD1+, Birbeck granule-positive cells. These Langerhans were recognizable at 48 h after intradermal injection and reached maximum numbers by 4 d. During this period the number of epidermal Langerhans cells remained relatively constant. No increment in dermal Langerhans cells occurred when GLM-CSF was injected by the subcutaneous route. No appreciable increase in the numbers of T cells and monocytes was noted, and granulocytes and eosinophils were largely present within the dermal microvasculature. 4-mm punch biopsies taken from injected sites and adjacent controls were compared in terms of the rapidity of wound healing. 22 of 26 sites demonstrated more rapid filling and hemostasis, whereas four were equivalent to controls. We conclude that rGM-CSF, when introduced into the skin, leads to enhanced keratinocyte growth, the selective recruitment of Langerhans cells into the dermis, and enhanced wound healing of the prepared site. There was no evidence of an enhanced cell-mediated response to Mycobacterium leprae, and bacillary numbers remained unchanged.
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PMID:Novel responses of human skin to intradermal recombinant granulocyte/macrophage-colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing. 158 89

Mycobacterium leprae, in contrast to BCG, failed to trigger any chemiluminescence (CL) response in mononuclear cells from either leprosy patients or healthy subjects, a deficit not reversed by either interferon-gamma or GM-CSF. Chemiluminescence responses induced without mycobacteria or with BCG were found to be lower in leprosy patients than in controls. M. leprae were also less well phagocytosed than BCG. However, there was a significant difference in phagocytosis between healthy and tuberculoid leprosy subjects. Phagocytosis was not altered by the addition of either lymphokine, and no major differences between healthy subjects and patients were observed. Preincubating mononuclear cells with anti-mycobacteria antibodies (lepromatous patients' sera) did not increase the CL response nor the phagocytosis of M. leprae or BCG.
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PMID:M. leprae- and BCG-induced chemiluminescence response of monocytes from leprosy patients and healthy subjects: effects of gamma-interferon and GM-CSF. 180 41

The effect of human recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) on the uptake and intracellular growth of Mycobacterium tuberculosis in human macrophages was investigated. GM-CSF was found to reduce growth of M. tuberculosis in human monocyte-derived macrophages in vitro, as compared to untreated cells. The decrease in intracellular growth of the tubercle bacilli did not depend on generation of reactive oxygen species, inasmuch as treatment with scavengers did not affect the ability of GM-CSF to restrict mycobacterial growth in macrophages.
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PMID:Granulocyte-macrophage colony-stimulating factor restricts growth of tubercle bacilli in human macrophages. 211 96

Both smooth transparent (SmT) and smooth domed-opaque (SmD) colonial variants were obtained from a strain of Mycobacterium avium isolated from a patient with AIDS. The two variants showed similar biochemical characteristics but SmT bacteria proliferated better than SmD bacteria inside human macrophages and were much less capable than the SmD variant of inducing the release of IL-1 beta, IL-6, TNF-alpha, GM-CSF and G-CSF, after incubation for either 3 or 6 days. As cytokines are important extracellular signals for immune cells, the lack of induction observed in SmT-infected macrophages may be one of the pathogenic mechanisms of M. avium.
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PMID:Induction of IL-1 beta, IL-6, TNF-alpha, GM-CSF and G-CSF in human macrophages by smooth transparent and smooth opaque colonial variants of Mycobacterium avium. 750 78

Although Mycobacterium avium is usually nonpathogenic in healthy individuals, in vitro infection of macrophages (M phi) from the majority of healthy donors induces death of the cells 2 wk after infection; this effect is in contrast to noninfected M phi, which survive for months in culture. We demonstrate here that treatment of normal M phi with indomethacin further shortens the life of these cells to 48 h after infection with M. avium. Indomethacin treatment of the M phi also prevents M. avium-dependent accumulation of mRNA-encoding plasminogen activator inhibitor type-2 (PAI-2), an inhibitor of urokinase-type plasminogen activator. Occurrence of nuclear condensation and DNA fragmentation in M phi pretreated with indomethacin and infected with M. avium indicates that the early death of these cells is caused by apoptosis. In contrast, priming of M phi with GM-CSF significantly prolongs their survival after M. avium infection and enhances M. avium-induced accumulation of PAI-2 mRNA. Most importantly, addition of PAI-2 is sufficient to prevent apoptosis of M phi infected with M. avium in the presence of indomethacin. Finally, M phi not treated with indomethacin also die of apoptosis 7 to 10 days after M. avium infection and can be rescued by PAI-2. These studies indicate that production of PAI-2 by normal M phi as a consequence of M. avium infection inhibits programmed cell death, a mechanism that might serve to prevent the spread of the infection.
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PMID:Plasminogen activator inhibitor type 2 prevents programmed cell death of human macrophages infected with Mycobacterium avium, serovar 4. 763 97

Organisms belonging to the Mycobacterium avium complex (MAC) are common pathogens in immunosuppressed and AIDS patients. This paper reviews the role of cytokines in the pathogenesis of MAC infection. MAC organisms mainly infect monocytes and macrophages, and the effect of HIV infection on susceptibility of macrophages to MAC infection is largely unknown. Both GM-CSF and tumour necrosis factor-alpha can induce mycobacteriostatic/mycobactericidal activity in MAC-infected macrophages. The activity of interferon-gamma on mycobacterial infection appears to be dependent on the type of macrophage: in murine peritoneal and human monocyte-derived macrophages, interferon-gamma does not inhibit the intracellular growth of MAC, whereas in intestinal macrophages interferon-gamma results in inhibition of MAC. Transforming growth factor-beta 1, interleukin-10 and interleukin-6 have all been shown to counteract the immunoactivating cytokines and MAC survival may be due to induction of these inhibitory cytokines within the macrophage. GM-CSF has been given to patients with disseminated MAC infection. Isolated macrophages from these patients demonstrated increased superoxide anion production and enhanced mycobacteriostatic/cidal activity compared with macrophages isolated from the same patients before GM-CSF treatment. These results suggest that GM-CSF may have potential in the treatment of MAC infection.
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PMID:Potential role of cytokines in disseminated mycobacterial infections. 787 49

The acquisition of a bactericidal activity by the cellular immune system is one of the mechanisms of prime importance for the development of the cellular resistance to infection. It involves the specific recognition of the pathogenic microorganism associated with the direct or indirect activation of effector cells. The in vivo type of replication of the infectious microorganism provides the adaptive response of the host. This response differs according to extracellular or intracellular multiplying microorganism. The acquired resistance to extracellular multiplying bacteria (ie, capsulated bacteria) is linked to the B cell production of specific antibodies that are associated with the activated complement fragments, that enable bacterial opsonization, activation and recruiting of polymorphonuclear phagocytes. These cells did acquired a greater capacity to ingest and to kill bacteria at sites of infection. Such phenomenon could be also associated with acute purulent necrotizing lesions. On the other hand, intracellular multiplying bacteria are mostly associated with chronic granulomatous non pyogenic lesions, and such bacteria are also able to survive and to replicate into the non activated professional mononuclear phagocytes. The acquired resistance against such bacteria is linked to the occurrence of a non specific bactericidal capacity of macrophages, that inhibit and/or kill replicative intracellular microorganisms. Such macrophage bactericidal capacity is dependent upon the gradual and stepwise cellular activation provided by several extracellular and membrane associated signals. Sequential signals are produced by the specific recognition of committed T CD4+ lymphocytes mediated by the infected macrophages through the MHC class 2 restriction of the peptide presentation. One of the major signal of cellular communication to induce macrophage priming involves the production of Interferon gamma (IFN gamma). Secondary signals are needed to induced full macrophage activation defined by phenotypic, metabolic and functional alterations which include their acquired increase capacity to kill intracellular bacteria and tumor cells. Secondary signals involve the production of cytokines such as TNF alpha, IL2 and GM-CSF being transduced by bacterial cell wall products (such as lipopolysaccharide, teichoic acid, or lipoarabinomanan) or by the calcitriol pathway recently described during mycobacterial infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Bactericidal activity of cells of the immune system]. 812 21

A 31-year-old woman presented with fever and arthralgia. Despite treatment with antimicrobials and corticosteroids, her symptoms persisted. A diagnosis of myelodysplastic syndrome (MDS)-refractory anemia (RA) was made by pancytopenia, dysplasia, and trisomy 8. Cultures of bone marrow, blood, and gastric juice showed Mycobacterium avium-intracellulare (MAI). She was treated with antimycobacterial drugs and recombinant human G-CSF/M-CSF and showed an initial response, but spike fever recurred and pancytopenia progressed. Hepatosplenomegaly and marked retroperitoneal lymphadenopathy were revealed, indicating further dissemination of MAI. Treatment with recombinant human GM-CSF and very-low-dose cytosine arabinoside, was started but was not effective. This case showed significant reduction in peripheral blood T-lymphocytes, especially the CD4+ population, and low immunoglobulin levels. Immunodeficiency state associated with long-term steroid therapy and MDS seemed to contribute to the development of the disseminated infection with MAI.
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PMID:Disseminated Mycobacterium avium-intracellulare infection in a patient with myelodysplastic syndrome (refractory anemia). 817 3

In this study we found that addition of a range of doses of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), or granulocyte-macrophage colony stimulating factor (GM-CSF) to cultures of bone marrow-derived murine macrophages infected with the 25291 strain of Mycobacterium avium gave rise to varying degrees of bacteriostasis. In contrast, similar treatment with interleukin-4 (IL-4) or IL-6 had no effect. However, when similar experiments with the former set of cytokines were performed using a panel of M. avium isolates, substantial isolate-to-isolate variation was observed. In cultures containing IFN-gamma, synthesis of substantial levels of reactive nitrogen intermediates was observed; however, neither these materials, nor reactive oxygen intermediates, were found to be responsible for observed bacteriostasis. In further experiments, in which the culture medium was supplemented with various concentrations of a weak acid or a weak base in order to influence the pH of macrophage intracellular compartments, it was found that the presence of the weak acid augmented the activity of IFN-gamma, whilst the weak base counteracted this effect. These data support the hypothesis, therefore, that the bacteriostatic effect of IFN-gamma against the growth of M. avium, rather than depending on reactive radical production, is mediated through acidification of the infected phagosome, perhaps through activation of proton pumps in the phagosomal membrane.
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PMID:Effector mechanisms involved in cytokine-mediated bacteriostasis of Mycobacterium avium infections in murine macrophages. 828 11


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