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)

Interleukin-6 (IL-6) is a cytokine produced by a number of cells, including macrophages, and is directly involved in the inflammatory response. The production of IL-6 can be stimulated by monokines such as IL-1 and tumor necrosis factor (TNF). Mycobacterium avium complex organisms frequently cause disseminated disease in patients with AIDS. M. avium is an intracellular bacterium that that mainly infects macrophages. Treatment of M. avium-infected macrophage monolayers with recombinant IL-6 decreased the ability of TNF to activate cultured macrophages to inhibit growth of or kill intracellular M. avium (68% +/- 14% decrease in intracellular killing compared with that in monolayers not treated with IL-6). To further evaluate whether this effect was dependent on the down regulation of membrane receptors to TNF, we examined 125I-TNF binding to macrophages previously exposed to IL-6: the expression of TNF receptors was decreased by 78% +/- 9%. The effect of IL-6 on TNF receptors was observed after 4 h and was reversible. Infection of macrophages with different M. avium serovars was associated with release of IL-6, and IL-6 production peaked at 48 h after infection in concentrations ranging from 328 +/- 87 ng/10(5) cells to 907 +/- 224 ng/10(5) cells. IL-6 did not have any influence on the rate of growth of the tested strains of M. avium within or outside macrophages. These results suggest that release of IL-6 by M. avium-infected macrophages may influence the host's immune response and the outcome of the disease.
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PMID:Interleukin-6 antagonizes tumor necrosis factor-mediated mycobacteriostatic and mycobactericidal activities in macrophages. 132 56

Because pancreatitis has been reported frequently in adults with human immunodeficiency virus infection, we sought to determine the incidence of pancreatitis in children with acquired immunodeficiency syndrome by reviewing all records of children with AIDS, their serum amylase and lipase levels, and the factors associated with pancreatitis through a case-control analysis. During a 6-year period pancreatitis developed in 9 (17%) of 53 pediatric patients with AIDS. Six children had vertical transmission of infection and three patients had acquired HIV infection through contaminated blood products. Pancreatitis developed at a median age of 5.2 years (range 1.2 to 20 years). All patients had vomiting and abdominal pain. When the patients were first seen, lipase values were elevated more than amylase values (p = 0.028). Amylase and lipase levels declined at comparable rates. In the case-control analysis, pentamidine isethionate was significantly associated with pancreatitis (p = 0.02); the risk was greater in patients who received pentamidine isethionate and had absolute CD4 T-lymphocyte counts less than 100 cells/mm3 (p = 0.001). Infections associated with the onset of pancreatitis included cytomegalovirus (4), Cryptosporidium (1), Pneumocystis carinii pneumonia (3), and Mycobacterium avium intracellulare (1). Coinfection with cytomegalovirus was associated with a protracted course in four children. Ultrasonographic examination demonstrated biliary ductal dilatation 6 months after the onset of pancreatitis in one child. Seven children have died at a mean of 8 months after the initial onset of pancreatitis; the one living child has survived 5 months from the onset of pancreatitis. We conclude that pancreatitis is common in pediatric patients with AIDS and may be related to pentamidine isethionate exposure, especially when absolute CD4 T-lymphocyte counts are less than 100 cells/mm3. Serum amylase levels do not always accurately predict the onset of pancreatitis; serum lipase levels should be measured in children with symptoms. The onset of pancreatitis in an HIV-infected child is a poor prognostic indicator.
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PMID:Pancreatitis in pediatric human immunodeficiency virus infection. 137 Sep 62

In a randomized double-blind study, nine mycobacteremic patients with AIDS-related disseminated Mycobacterium avium complex (MAC) infection received clarithromycin or placebo in addition to a basic regimen that included isoniazid, ethambutol and clofazimine. All four patients receiving clarithromycin showed blood culture conversion and clinical response. Of the five patients treated without clarithromycin, two showed resolution of mycobacteremia and clinical response, while another two died without having shown response. The remaining patient deteriorated until a switch from placebo to clarithromycin led to blood culture conversion and rapid clinical improvement. After finishing six weeks of intensive treatment, clarithromycin was given in an open maintenance phase to all patients, initially in combination with rifabutin for 24 weeks and then alone. One patient had a relapse of MAC infection while receiving clarithromycin alone. The relapse was associated with acquired resistance to the drug. Clarithromycin appears to be a promising component of multi-drug therapy for patients with MAC infection. Monotherapy can lead to drug resistance.
Infection
PMID:Effectiveness of the macrolide clarithromycin in the treatment of Mycobacterium avium complex infection in HIV-infected patients. 142 83

An effective intracellular concentration of an antimicrobial agent is essential for therapy of infections caused by organisms of the Mycobacterium avium complex. We previously reported on the effect of the combination of azithromycin and tumor necrosis factor (TNF) against M. avium infection in macrophages. We now report that stimulation of macrophages either with recombinant human gamma interferon (IFN-gamma, 10(2) U/ml) or with recombinant human TNF-alpha (10(2) U/ml) resulted in an increase in the intracellular concentration of azithromycin by approximately 200% within 3 h, compared with the concentration in unstimulated macrophages. Infection of macrophages with M. avium complex led to a decrease in the uptake of [14C]azithromycin by infected cells, compared with that by uninfected controls. Stimulation of infected macrophages with recombinant IFN-gamma or TNF-alpha overcame the inhibitory effect associated with infection. These results suggest that the increased bactericidal activity of the TNF-alpha-azithromycin or IFN-gamma-azithromycin combination against M. avium is related to enhanced uptake of the antibiotic by the stimulated phagocyte.
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PMID:Stimulation with cytokines enhances penetration of azithromycin into human macrophages. 166 56

Infection with the human immunodeficiency virus (HIV) results in progressive depletion of the CD4 subset T-lymphocytes and the development of opportunistic infections and certain malignancies. Charts were reviewed for 185 HIV-infected individuals with 265 AIDS-defining illnesses (ADIs) who had T-lymphocyte subset analyses performed within 2 months prior to or 1 month following the diagnosis. Also included were 22 HIV-infected patients with oral candidiasis and 20 with asymptomatic infection. Significant differences in CD4 lymphocyte numbers were observed between the 12 ADIs, oral candidiasis, and asymptomatic infection, allowing them to be grouped into five general categories, based on mean CD4 count: (a) asymptomatic infection, CD4 greater than 500/mm3; (b) oral candidiasis and tuberculosis, range 250-500/mm3; (c) Kaposi's sarcoma, lymphoma, and cryptosporidiosis, range 150-200/mm3; (d) Pneumocystis carinii pneumonitis, disseminated Mycobacterium avium complex, herpes simplex ulceration, toxoplasmosis, cryptococcosis, and esophageal candidiasis, range 75-125/mm3; (e) cytomegalovirus retinitis, less than 50/mm3. Our data concur with clinical impressions and provide a basis for interim treatment and prophylaxis recommendations.
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PMID:Predictive value of CD4 lymphocyte numbers for the development of opportunistic infections and malignancies in HIV-infected persons. 167 19

The activity of clarithromycin in combination with ethambutol and rifampicin was tested at concentrations achievable in serum against 20 strains of Mycobacterium avium complex. The combination of clarithromycin plus rifampicin showed inhibition of 11 of the strains and bactericidal synergism against seven of the strains. When ethambutol was added, a bactericidal effect was observed against 16 strains. On the basis of these in vitro data it seems that clarithromycin in combination with rifampicin and ethambutol may be a promising drug for the effective treatment of infections caused by M. avium complex.
Infection
PMID:In vitro testing of clarithromycin in combination with ethambutol and rifampicin against Mycobacterium avium complex. 183

Patients with the acquired immune deficiency syndrome (AIDS) frequently develop hepatic dysfunction. Although hepatic injury may indirectly result from malnutrition, hypotension, administered medications, sepsis, or other conditions, the hepatic injury is frequently due to opportunistic hepatic infection, directly related to AIDS. Infection with Mycobacterium avium intracellulare typically occurs in patients with advanced immunocompromise and with systemic symptoms due to widely disseminated infection. In contrast, hepatic tuberculosis often occurs with less advanced immunocompromise. Cytomegaloviral infection may produce a hepatitis. Cytomegaloviral and cryptosporidial infections have been implicated as causes of acalculous cholecystitis and of a secondary sclerosing cholangitis. About 10-20% of patients with AIDS have chronic hepatitis B infection. These patients tend to develop minimal hepatic inflammation and necrosis. The clinical findings in patients with hepatic cryptococcal infection are usually due to concomitant extrahepatic infection. Hepatic histoplasmosis usually develops as part of a widely disseminated infection with systemic symptoms. Hepatic involvement by Kaposi's sarcoma is rarely documented ante mortem because an unguided liver biopsy is an insensitive diagnostic procedure. Patients with non-Hodgkin's lymphoma of the liver typically have lymphadenopathy, hepatomegaly, and systemic symptoms. As a pragmatic approach, patients with liver dysfunction and HIV-related disease should have a sonographic or computerized tomographic examination of the liver. Patients with dilated bile ducts should undergo endoscopic retrograde cholangiopancreatography because opportunistic infection may produce biliary obstruction. Patients with a focal hepatic lesion should be considered for a guided liver biopsy. Patients with a significantly elevated serum alkaline phosphatase level should be considered for a percutaneous liver biopsy. When performed for these indications, liver biopsy will demonstrate a significant disease involving the liver in about 50% of patients with AIDS and in about 25% of patients who are HIV seropositive but who are not known to have AIDS. The clinical impact of a diagnostic biopsy is blunted by a lack of efficacious therapy for many opportunistic infections.
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PMID:Hepatobiliary manifestations of the acquired immune deficiency syndrome. 198 33

Mycobacterial disease is a major part of the spectrum of opportunistic infections (OIs) associated with HIV infection. Mycobacterium avium intracellulare (MAI) and Mycobacterium tuberculosis are the most common mycobacterial pathogens afflicting HIV-positive patients. Infection with MAI tends to be an OI of advanced AIDS, and the results of treatment are frequently unsatisfactory. M. tuberculosis tends to attack patients much earlier in the course of their HIV disease, responds to standard treatment, and is the most contagious of the life-threatening HIV-related pathogens. This article provides concise information about the management of mycobacteriosis in the context of HIV infection. It is directed especially at primary care physicians. Emphasis is on clinical manifestation, diagnosis, therapy, and prevention.
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PMID:Mycobacterial disease associated with HIV infection. 200 73

Bacterial infections of the gastrointestinal tract (GI tract) in patients with AIDS are characterized by bacteremia and persistence of the pathogen. Infections with Salmonella typhi murium are common. Infections with atypical mycobacteria (Mycobacterium avium intracellulare complex) mimic Whipple's disease both clinically and histologically; at present no established therapy is available. Among the parasitic diseases of the GI tract, cryptosporidial infection in AIDS patients, predominantly in tropical countries, plays an important role for epidemiological reasons. It leads to profuse watery diarrhea that does not respond to drug treatment. The AIDS-specific Kaposi's sarcoma and non-Hodgkin's lymphoma may have manifestations in the GI tract. Rare complications of these tumors are bleeding, diarrhea and ileus.
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PMID:[Gastrointestinal manifestations of AIDS. 2: Bacterial and vh parasitic infections, malignant tumors]. 205 81

Intracerebral inoculation of mice with Theiler's murine encephalomyelitis virus results in an intense inflammatory response of mononuclear leukocytes which infiltrate into the central nervous system. Resistant strains of mice have the ability to clear virus whereas susceptible strains become infected persistently and are associated with chronic demyelination which is proposed to be immune-mediated. In an attempt to better understand the role of the immune response during demyelination, mononuclear leukocytes were isolated from the central nervous system of infected mice and stained by an immunoperoxidase technique with anti-Thy-1.2, anti-L3T4, anti-Lyt-2 and anti-MAC-1 mAb. Infection of susceptible SJL/J mice resulted in a biphasic immune response which peaked on days 7 and 27 post-infection. In contrast, a single peak (day 7) was observed in resistant C57BL/10SNJ mice. The presence of Thy-1.2, L3T4, and MAC-1+ cells was similar between the two strains. However, although the number of Lyt-2+ cells peaked on day 7 in C57BL/10SNJ mice, they were not detected in SJL/J mice until 14 days post-infection and gradually increased in number over the course of infection. To further study the role of T cells in demyelination, serial frozen sections of brain and spinal cord were stained for the presence of Lyt-2 and L3T4+ cells in the lesions of chronically infected SJL/J mice. L3T4+ cells were observed predominantly in perivascular regions while Lyt-2+ cells were observed infiltrating the parenchyma. These results provide further evidence that Lyt-2+ lymphocytes are important in the mechanism of susceptibility/resistance to Theiler's murine encephalomyelitis virus-induced demyelination.
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PMID:Characterization of the inflammatory response in the central nervous system of mice susceptible or resistant to demyelination by Theiler's virus. 249 23


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