Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026916 (MAC)
 5,226 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Organisms belonging to the Mycobacterium avium complex are the most common bacteria isolated from patients with AIDS. In these patients, M. avium is associated with disseminated disease, and bacteria are found within macrophages in the liver and spleen. To examine the potential of M. avium infection of a nonprofessional phagocyte, the murine fibroblast cell line (L929 cells) are infected with strain 101 (serotype 1) of M. avium. The duplication time for the intracellular bacteria was approximately 36 hr. Progressive intracellular growth ultimately resulted in the destruction of infected cells (after approximately 12 days in culture). Supernatant obtained from infected L929 cells contained interferon-beta (IFN beta) and granulocyte macrophage colony stimulating factor (GM-CSF) (50 +/- 12 ng/10(5) cells and 63 +/- 18 pg/10(5) cells, respectively, by 18 hr). IFN beta could be detected by 3 hr after infection, while GM-CSF was first detected by 6 hr. Release of IFN beta by infected L929 cells could subsequently stimulate NK cells, but not macrophages, to lyse infected L929 cells. These data using L929 cells suggest that M. avium may invade fibroblasts during the course of the infection and that fibroblast infection may trigger NK cell-mediated cytotoxicity against the infected fibroblasts.
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PMID:Infection of "nonprofessional phagocytes" with Mycobacterium avium complex. 191 58

The long term survival of peripheral blood derived human macrophages (M phi) from normal, healthy donors after infection with Mycobacterium avium intracellulare (MAI) correlates with the increased induction of TNF-alpha and IL-6 mRNA and protein by the infected M phi. This conclusion is based on the following observations: M phi from approximately 30% of the blood donors in our study die 3 to 4 days after inoculation (MAI-growth nonsupportive (NS], whereas M phi from the other donors survive inoculation with MAI for 7-10 days (MAI-growth supportive (S)). S-type M phi when infected with MAI had markedly increased amounts of TNF-alpha and IL-6 mRNA and protein when compared to NS-type M phi. The effect of LPS on the induction of TNF-alpha mRNA and protein was also significantly enhanced in S-type M phi in comparison to NS cells. In contrast, IL-1 beta mRNA and protein production had similar increases in both donor types when infected with MAI or stimulated with LPS. The phenotype of the donors in the amount of TNF-alpha and IL-6 produced in response to MAI infection remained stable for a period of more than 1 yr. Pretreatment of NS M phi with recombinant human granulocyte-macrophage-CSF, but not IFN-gamma, however, converted NS M phi into a S-type cell phenotype. These granulocyte-macrophage-CSF pretreated NS M phi survived infection with MAI for a longer period of time and also had increased production of both TNF-alpha and IL-6 mRNA and protein. Cultures of S-type M phi infected with MAI had higher numbers of intracellular bacteria when compared to cultures of NS-infected M phi. Thus, increased survival of MAI-infected human M phi in vitro is correlated to increased production of TNF-alpha and IL-6 in response to infection with MAI.
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PMID:Survival of human macrophages infected with Mycobacterium avium intracellulare correlates with increased production of tumor necrosis factor-alpha and IL-6. 194 Mar 76

Organisms belonging to the Mycobacterium avium complex (MAC) are associated with life-threatening bacteremia in patients with the acquired immunodeficiency syndrome (AIDS). As these organisms survive within macrophages, we examined the ability of recombinant human granulocyte-monocyte colony-stimulating factor (GM-CSF) to activate human monocyte-derived macrophages to inhibit the intracellular growth or kill the most mouse-virulent MAC strain in our collection that belongs to serotype 1. While unstimulated cells did not inhibit intracellular growth of MAC, macrophages activated by GM-CSF (10-10(4) U/ml) inhibited or killed up to 58 +/- 5% of the initial inoculum. This activation was dose-dependent, with maximal change occurring with a dose of 100 U/ml after 72 hr exposure. Inhibition or killing was demonstrated if GM-CSF was given both before or after establishment of infection. The combination of GM-CSF (10(2) U/ml) plus TNF (10(2) U/ml) augmented macrophage killing (range, 31 +/- 4%) compared with GM-CSF (10(2) U/ml) alone, but the combination of recombinant human interferon-gamma (IFN gamma) plus GM-CSF resulted in a significant decrease in intracellular inhibition of growth or killing (13.3 +/- 2%) compared with 57.7 +/- 5% obtained with GM-CSF alone. These results indicate that: 1) GM-CSF can activate macrophages to inhibit intracellular growth or kill MAC; 2) killing may be augmented by TNF; and 3) IFN gamma may impair GM-CSF-dependent macrophage activation.
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PMID:Recombinant granulocyte-macrophage colony-stimulating factor activates human macrophages to inhibit growth or kill Mycobacterium avium complex. 211 63

Vitamin D3 (D3) has been shown to activate several macrophage functions. To determine whether D3 could activate macrophages to kill or inhibit intracellular growth of Mycobacterium avium complex (MAC), human monocyte-derived macrophages were treated with D3 (10(-7), 10(-8), and 10(-9) M) 24 hr before or for 48 hr after MAC infection. All three concentrations were associated with inhibition of growth or killing of MAC in a dose-dependent fashion (28 +/- 4% and 22 +/- 3% of killing and inhibition of growth, respectively, at pharmacological concentrations) when added to the monolayer before injection or 60.4 +/- 6%, 50.4 +/- 3%, and 41.4 +/- 6%, respectively, when added to the monolayers after infection. We found that D3-treated macrophages produced increased concentrations of tumor necrosis factor (TNF) and granulocyte-monocyte colony stimulating factor (GM-CSF). Subsequently, macrophages were activated by D3 in the presence of anti-TNF or anti-GM-CSF antibody: At 10(-9) M of D3 there was no inhibition of D3-dependent macrophage activation by anti-TNF antibody, whereas anti-GM-CSF antibody was associated with 100% inhibition. At 10(-8) M of D3, anti-TNF antibody inhibited 35 +/- 6% of killing, and anti-GM-CSF antibody was associated with 100% inhibition. At 10(-7) M of D3, anti-TNF antibody inhibited 58 +/- 4% and anti-GM-CSF antibody 89 +/- 3% of killing. D3 treatment is associated with anti-MAC activity in human macrophages, and this activity appears to be mediated by both TNF and GM-CSF.
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PMID:1,25 Dihydroxyvitamin D3-dependent inhibition of growth or killing of Mycobacterium avium complex in human macrophages is mediated by TNF and GM-CSF. 218 43

To evaluate the impact of anesthetics on the evolution of a cerebral injury, 33 rabbits were subjected to a cryogenic brain lesion, followed by 10 h of anesthesia with 1 MAC halothane or isoflurane (n = 11 each) or with an equipotent dose of pentobarbital (n = 11). The lungs were ventilated to a PaCO2 = 30-35 mmHg with O2/air and normothermia was maintained. Intracranial pressure (ICP), mean arterial pressure (MAP), central venous pressure (CVP), arterial blood gases, and pH, osmolality, and other blood chemistries were recorded. Fifteen minutes after surgery, a left parietal injury was produced with liquid N2. A MAP greater than 70-75 mmHg was maintained throughout the study, using angiotensin II as needed, and CSF was removed if severe intracranial hypertension (ICP greater than 30 mmHg) threatened to reduce cerebral perfusion pressure (CPP = MAP-ICP) below 40 mmHg. 10 h after injury, the animals were killed, and edema formation assessed by: A) the wet weight of the two hemispheres; B) water content (%H2O; wet-dry weight) of the posterior aspect of the hemispheres; and C) specific gravity (SpGr) of tissue samples taken adjacent to and distant from the lesion. Animals given pentobarbital had higher MAP's until 3 h after the lesion had been induced. There were no subsequent intergroup differences in MAP, and no differences at any time in CVP, PaO2, PaCO2, pH, total fluids, or urine output. ICP increased in all animals, but with no significant intergroup differences (ICP in halothane animals was numerically lower). There were no clear differences in the incidence of ventricular drainage (1 halothane, 5 isoflurane, 3 pentobarbital; P = 0.16). In spite of CSF drainage and angiotensin, CPP
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PMID:A comparison of the effects of halothane, isoflurane, and pentobarbital anesthesia on intracranial pressure and cerebral edema formation following brain injury in rabbits. 280 14

An anti-rabies IgM antibody capture radio immunoassay was used to test serum and cerebrospinal fluid from 37 dogs held in quarantine for suspicion of rabies. Rabies was confirmed in dogs that died by mouse inoculation and subsequent examination of mouse brains by fluorescent antibody technique to detect rabies antigen. The mean counts per minute (CPM) of iodinated anti-rabies gamma globulin coupled IgM rabies antibody in CSF and serum from rabid dogs were significantly higher than in CSF and serum from non-rabid dogs. Mean CPM from rabid dogs was greater in CSF than in sera, in contrast with non-rabid dogs, from which mean cpm was higher in sera than CSF, suggesting that antibody may have been synthesized in the CSF. To evaluate this test further, a dog was infected by rabies virus, and serial serum and CSF specimens were collected until the time of death. IgM anti-rabies antibody developed in the CSF and serum 29 days following infection, and rose just before the dog died of rabies on day 34. The rabies MAC RIA is potentially useful as a diagnostic method in quarantined dogs with rabies-like illness. Perhaps more importantly, it may be applied to better understand the immunopathogenicity of rabies.
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PMID:Anti-rabies virus IgM in serum and cerebrospinal fluid from rabid dogs. 357 84

In this report we report that recombinant human monocyte-macrophage colony-stimulating factor-1 (CSF-1) induces resident murine peritoneal cells (PCs) to transcribe several inflammatory cytokine genes, including interleukin (IL)-1 alpha, IL-1 beta, IL-6, and granulocyte-macrophage CSF in a dose-dependent and time-related manner. Peak mRNA levels were seen between 4 and 6 h. CSF-1 did not modulate the expression of tumor necrosis factor-alpha mRNA. The serum content of the culture medium appeared to regulate both the extent of CSF-1-induced gene transcription and the adherence properties of the cells. Decreasing the serum concentration significantly reduced CSF-1-induced transcription and was associated with the rapid spreading of the majority of the adherent cells. This reduced sensitivity to CSF-1 was paralleled by a markedly lower levels of c-fms mRNA encoding the CSF-1 receptor. Induced gene transcription was followed by the release of large quantities of IL-6 only. IL-1 activity remained associated with the cells. Neither supernatant nor cell lysate granulocyte-macrophage CSF activity was inducible above the low levels associated with control cultures. Evidence that the mononuclear phagocytes, as opposed to B or T cells, were the targets of CSF-1 was obtained in two ways: (1) PCs from B6 scid/scid and NOD scid/scid mice consisting of 78-86% MAC-1+, F4/80+ cells and few B or T cells, as shown by flow cytometry analysis, released 5- to 10-fold more IL-6 in response to CSF-1 stimulation than B6 PCs, which contained approximately 30% double-positive cells, and (2) pretreatment of B6 PCs with antibodies to the CSF-1 receptor blocked the CSF-1-induced secretion of IL-6. These data suggest that CSF-1 primes noninflammatory mononuclear phagocytes for a role in inflammatory responses but does not provide the necessary signals for either secretion or translation of all cytokines equally.
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PMID:The potential role of the macrophage colony-stimulating factor, CSF-1, in inflammatory responses: characterization of macrophage cytokine gene expression. 761 11

A wide variety of pathologies afflicting the CNS is see in patients infected with the human immunodeficiency virus. We report the case of relapsing meningoencephalitis caused by Mycobacterium avium intracellulare (MAI) in a homosexual male with the acquired immunodeficiency syndrome in whom repeated use of polymerase chain reaction was required to detect MAI-specific DNA in the cerebrospinal fluid. Successful responses to early empirical antibiotic combination treatment, including the drugs clarithromycin and rifabutin, were demonstrated by clinical, EEG, and CSF improvement during an 8-month period. To our knowledge, this study presents the first known patient with the acquired immunodeficiency syndrome effectively treated for MAI meningoencephalitis and suggests that modern antimycobacterial combination therapy may improve the poor prognosis of CNS infections with nontuberculous mycobacteria.
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PMID:Successful treatment of meningoencephalitis caused by Mycobacterium avium intracellulare in AIDS. 789 10

Cytomegalovirus encephalitis (CMVE) is frequently diagnosed only at postmortem because its specific clinical features have not been fully identified. We have described the clinical, radiologic, and laboratory features of CMVE in a retrospective review of 14 autopsy-confirmed cases of CMVE and compared them with a control group of demented acquired immunodeficiency syndrome (AIDS) patients without CMVE. CMVE was more common among homosexual men, and a subacute onset was more typical (mean duration of presenting symptoms was 3.5 weeks versus 18 weeks in demented controls). Median survival times were 4.6 weeks for CMVE and 28 weeks for controls. CMVE was accompanied by prominent systemic CMV infection at autopsy, including CMV adrenalitis (92%), CMV pneumonitis (42%), systemic Mycobacterium avium intracellulare (MAI; 58%), and CMV retinitis (58%). Hyponatremia and MAI bacteremia were found in 58% of CMVE cases. Polymerase chain reaction (PCR) of CSF samples identified CMV genome in 33% of CMVE cases. CMVE was associated with periventricular enhancement on CTs and periventricular lesions with meningeal enhancement on MRI scans. CMVE should be particularly suspected in homosexual men presenting with subacute encephalopathy who have had AIDS for more than 1 year and have a history of systemic CMV infection. Other features supporting the diagnosis of CMVE include periventricular lesions, hyponatremia, and identification of CMV genome in CSF by PCR.
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PMID:Cytomegalovirus encephalitis in acquired immunodeficiency syndrome (AIDS). 814 23

We studied the response of monocytes/macrophages (MO/MAC) to lipopolysaccharide (LPS) and interferon-gamma (IFN gamma) stimulation with respect to the expression of macrophage-specific products, i.e. macrophage-colony-stimulating factor (M-CSF), c-fms, c-sis, tissue factors, transforming growth factor-beta (TGF beta) and interleukin-8 (IL8) after in vitro infection with HIV. The expression of IL8 was strongly elevated in HIV-infected cells, peaking at 4 h after stimulation with LPS. At that time, the uninfected control showed only weak expression of IL8. Other products, e.g. tissue factor, c-fms, M-CSF and TGF beta were not modulated after stimulation. In contrast to IL8, the expression of c-cis was significantly lower in infected cells after stimulation with IFN gamma compared to uninfected control cells.
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PMID:Expression of macrophage products after in vitro infection of human monocytes/macrophages with HIV. 844 75


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