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)

Peripheral blood mononuclear cells were isolated from noninfected control cows and from cows with either subclinical or clinical paratuberculosis (Johne's disease). Cells were incubated for 6, 12, 24, and 48 hours in complete medium with the following mitogens: concanavalin A (ConA), phytohemagglutinin-P (PHAP), pokeweed mitogen (PWM), and Escherichia coli lipopolysaccharide. In addition, cells were incubated for the same time periods with a Mycobacterium paratuberculosis sonicate (MpS) and live and heat-killed M. paratu-berculosis at 10:1 bacteria: cell ratio. After incubation, cell-free supernatants were analyzed for gamma-interferon (gamma-IFN) production. Cells from subclinical cows produced significantly higher levels of gamma-IFN than did cells from clinical animals after stimulation with mitogens ConA, PHAP, and PWM. Levels of gamma-IFN produced by noninfected control animals generally followed the pattern of those of subclinical animals. After incubation with MpS, significantly greater quantities of gamma-IFN were produced by cells isolated from subclinical animals than by cells from clinical cows and noninfected controls. Stimulation of cells with heat-killed or live M. paratuberculosis evoked a similar response. This study indicates that gamma-IFN production by peripheral blood mononuclear cells in response to M. paratuberculosis antigen may be an important diagnostic tool for the detection of paratuberculosis in subclinically affected animals.
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PMID:Production of gamma-interferon by peripheral blood mononuclear cells: an important diagnostic tool for detection of subclinical paratuberculosis. 884 78

The purpose of this project was to determine the effect of dexamethasone (DEX) treatment of tuberculous cows on antigen-stimulated gamma-interferon (gamma-IFN) production in a commercial Mycobacterium bovis gamma-interferon test (gamma-IFN test) developed for diagnosis of bovine tuberculosis. In the gamma-IFN test an enzyme-linked immunosorbent assay is used to detect bovine gamma-IFN in the plasma from whole blood samples cultured with M. bovis and Mycobacterium avium tuberculin purified protein derivatives (PPDs). DEX is a synthetic glucocorticoid commonly used as a potent anti-inflammatory agent, and experimentally as a model of stress-induced immunosuppression in cattle. DEX treatment has previously been associated with decreased lymphocyte response to mitogens in cattle, which led to the current hypothesis that DEX treatment would suppress stimulated gamma-IFN production resulting in false negative results in the gamma-IFN test. In replicate studies using naturally infected dairy cows, blood was drawn daily for at least 2 days prior to DEX treatment, during 3 days of DEX treatment, and for at least 9 days post-DEX. Results of the gamma-IFN test were evaluated by optical density (OD), and by three OD calculation methods: two different methods suggested by the manufacturer, and a method adapted from the evaluation of a bovine gamma-IFN test used in Australia. Prior to DEX treatment all cows had positive gamma-IFN tests by each calculation method. As early as 24 h after the first DEX injection a decline in PPD-stimulated gamma-IFN production was reflected in OD data for all cows. Calculated gamma-IFN test results were negative after DEX treatment for all but one cow, which was known to produce relatively large amounts of gamma-IFN as measured by this test. The degree of gamma-IFN suppression, and the number of days that gamma-IFN test results were negative after DEX treatment (1-8 days), varied by cow and by data calculation method. Treatment with DEX is associated with suppressed PPD-stimulated gamma-IFN production, which may be reflected as false negative results in the gamma-IFN test depending on the data calculation method applied. The results have implications for the management conditions and medical treatment schedule under which samples for the gamma-IFN test are collected.
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PMID:Effect of dexamethasone treatment of tuberculous cattle on results of the gamma-interferon test for Mycobacterium bovis. 894 67

The authors analysed some immunological criteria in leprosy patients diagnosed as borderline tuberculoid by the presentation of different grades of skin lesions as well as different grades of nerve involvement. Only 50% of the patients presented a single skin lesion and 58% had none or only one affected nerve. Nineteen patients (39.6%) showed a positive lepromin reaction (induration > or = 5 mm). Patients with a positive skin test had a greater number of skin lesions when compared with patients with a negative lepromin test. Fifty-seven percent of the patients were found to be positive using a lymphoproliferation test (LTT) in response to Mycobacterium leprae antigens. Positive LTT results did not correlate with the number of skin lesions, but patients unresponsive to LTT had a lesser extent of nerve involvement. Four out of 18 patients (22%) released high IFN gamma levels in PBMC culture stimulated by M. leprae. (mean U/ml +/- SD = 142 +/- 72). All of these 4 patients presented only one skin lesion, although three of them had more than one affected nerve. Nineteen out of 21 patients (90.5%) showed no anti-PGL-1 antibodies in their serum. The low levels of anti-PGL-1 antibodies among these patients confirmed their tuberculoid background even in those with multiple skin lesions. These findings seem to attribute an important role to IFN gamma in restraining the spreading of the infection in the skin, but IFN gamma may have an opposite effect on the nerves. The potential pathological effects of IFN gamma during the delayed type of hypersensitivity can be related to its ability to synergise with other inflammatory cytokines such as TNF alpha, IL-1 beta, and others.
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PMID:Borderline--tuberculoid leprosy: clinical and immunological heterogeneity. 903 99

In the present study, we evaluated whether the activation of a murine macrophage cell line (J774.1A) by treatment with recombinant murine tumor necrosis factor-alpha (rTNF-alpha) or recombinant murine interferon-gamma (rIFN-gamma) before or simultaneous with infection with Mycobacterium intracellulare would affect their ability to express lymphocyte function-associated antigen-1 (LFA-1) and to restrict growth and kill the ingested M. intracellulare. The data showed that the effect of lipopolysaccharide (LPS) in increasing the level of LFA-1 was the same in the presence or absence of M. intracellulare. The inability of M. intracellulare to affect the level of expression of LFA-1 was irrespective of the M. intracellulare to J774A.1 ratio. A significant increase in the expression of LFA-1 was observed when J774A.1 cells were prestimulated with IFN-gamma 1 day before the addition of the bacteria. The addition of IFN-gamma with M. intracellulare simultaneously, however, did not affect the expression of the adhesion molecules as compared with the IFN-gamma alone. Our results indicated no change in the level of LFA-1 on J774A.1 following exposure with TNF-alpha. We observed that preexposure with 10-10(4) IU/ml of TNF-alpha can significantly decrease the number of ingested M. intracellulare. Simultaneous addition of 10(3) and 10(4) IU/ml of TNF-alpha, however, did not have any mycobactericidal effect. This indicates that the TNF-alpha-induced killing by J774A.1 cells was relatively selective, depending on the concentration and the time of presence of TNF-alpha. The data may suggest that the uptake of M. intracellulare is carried out via other adhesion receptors when M. intracellulare and IFN-alpha are present simultaneously and that in the presence of TNF-alpha other surface receptors are involved in the uptake of M. intracellulare. Flow cytometry analysis of the spleen cells removed at various times from M. intracellulare-infected mice also indicated no change in the level of LFA-1 beta or MAC-1, a finding comparable with that of the J774A.1 cells.
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PMID:Treatment of an infected murine macrophage cell line (J774A.1) with interferon-gamma but not tumor necrosis factor-alpha or live Mycobacterium intracellulare alone modulates the expression of adhesion molecules. 905 12

The immune system has different possible ways of reacting to an antigen. The choice of an appropriate immune response is determined by the manner of antigen presentation, the amount of antigen, the localization of antigen uptake, the type of antigen presenting cell, the genetic predisposition of the individual and the presence of certain cytokines released by antigen presenting or other inflammatory cells. An immune response which is not not appropriate can lead to clinical symptoms or insufficient clearance of an infectious agent. This is well-illustrated in the example of lepra lepromatosa (insufficient, since humoral immune response to an intracellular agent) or lepra tuberculosa (complete clearance of Mycobacterium leprae). A decisive step for the type of immune response is the stimulation of different T-cell subpopulations. CD4 or CD8 T-cells can be further subdivided by a distinct cytokine production. So-called TH1 cells predominantly produce cytokines, which stimulate a cellular immune response (IFN gamma, IL-12, IL-2). In contrast, TH2 cells predominantly produce IL-4 and IL-5. These cytokines boost an IgE-mediated allergic reaction and inflammation. Although the TH1/ TH2 distinction is frequently not absolute, as overlaps can frequently be observed, this classification is useful for better understanding of immune reactions in various diseases. Moreover, since TH1- and TH2-related cytokines act antagonistically, therapeutic strategies are under development which strengthen e.g. a TH2 immune response in TH1 dominated diseases and vice versa.
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PMID:[Regulation of the immune response: the TH1/TH2 concept]. 913 32

Corynebacterium pseudotuberculosis, a gram-positive intracellular bacterial pathogen, is the etiological agent of the disease caseous lymphadenitis (CLA) in both sheep and goats. Attenuated mutants of C. pseudotuberculosis have the potential to act as novel live veterinary vaccine vectors. We have cloned and sequenced the aroB and aroQ genes from C. pseudotuberculosis C231. By allelic exchange, aroQ mutants of both C231, designated CS100, and a pld mutant strain TB521, designated CS200, were constructed. Infection of BALB/c mice indicated that introduction of the aroQ mutation into C231 and TB521 attenuated both strains. In sublethally infected BALB/c mice, both CS100 and CS200 were cleared from spleens and livers by day 8 postinfection. The in vivo persistence of these strains was increased when the intact aroQ gene was supplied on a plasmid in trans. Mice infected with TB521 harbored bacteria in organs at least till day 8 postinfection without ill effect. When used as a vaccine, only the maximum tolerated dose of CS100 had the capacity to protect mice from homologous challenge. Vaccination with TB521 also elicited protective immunity, and this was associated with gamma interferon (IFN-gamma) production from splenocytes stimulated 7 days postvaccination. The role of IFN-gamma in controlling primary infections with C. pseudotuberculosis was examined in mice deficient for the IFN-gamma receptor (IFN-gammaR(-/-) mice). IFN-gammaR(-/-) mice cleared an infection with CS100 but were significantly more susceptible than control littermates to infection with C231 or TB521. These studies support an important role for IFN-gamma in control of primary C. pseudotuberculosis infections and indicate that aroQ mutants remain attenuated even in immunocompromised animals. This is the first report of an aroQ mutant of a bacterial pathogen, and the results may have implications for the construction of aromatic mutants of Mycobacterium tuberculosis for use as vaccines.
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PMID:Attenuation and vaccine potential of aroQ mutants of Corynebacterium pseudotuberculosis. 923 53

Nitric oxide (NO) formed by the action of inducible form of nitric oxide synthase (iNOS), reacts with oxygen radical forming reactive nitrogen intermediate (RNI). NO and related RNI have been reported to possess antimycobacterial activity. Macrophages can inhibit the proliferation of Mycobacterium tuberculosis by producing NO. In murine models, the ability of macrophages to produce NO can determine the susceptibility of the host to M. tuberculosis and the virulence of M. tuberculosis. However, it is still not clear whether NO is involved in the defense mechanism against M. tuberculosis in humans. We have demonstrated that human peripheral blood mononuclear cells (PBMC) and airway epithelial cells can express iNOS mRNA expression and produce NO production in response to tubercle bacilli stimulation. Furthermore, H37Ra, avirulent strain of M. tuberculosis, induces a larger amount of NO in cultured PBMC than H37Rv, virulent strain, does. There was no difference in NO production between healthy volunteers and patients with tuberculosis. NO production in airway epithelial cells is closely related with IFN gamma concentration. The balance of stimulatory cytokines and inhibitory cytokines for NO production may play a critical role in the defense mechanism against M. tuberculosis considering that NO production is upregulated by IFN gamma, TNF alpha, and IL-1 beta and downregulated by IL-10 and TGF beta. The study of immune response to M. tuberculosis including NO production may give us a better understanding of the pathogenesis of tuberculosis.
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PMID:The role of nitric oxide in the immune response of tuberculosis. 944 84

Mycobacterium avium-intracellulare (MAI) pulmonary disease causes substantial morbidity in a population of older, HIV-negative women without preexisting lung disease. The cause for disease susceptibility in these patients is unknown, although their relative phenotypic homogeneity suggests the existence of a common, subtle immune deficiency. An investigation was undertaken to determine if these patients have a defect in their natural resistance-associated macrophage protein (NRAMP1) or interferon gamma receptor 1 (IFN-gammaR1) genes. A point mutation in murine nramp, an autosomal recessive gene controlling resistance to intracellular organisms, correlates with overwhelming Mycobacterium bovis infection in mice. The corresponding region in human NRAMP1, two coding polymorphisms and one promoter NRAMP1 polymorphism, as well as two IFN-gammaR1 polymorphisms, were analyzed to determine if an allele was present to correlate with disease. Genomic DNA was purified from eight women with MAI pulmonary disease and four controls. Regions of interest were amplified by PCR; three sites were analyzed by restriction fragment length polymorphisms, and three were analyzed using denaturing high-performance liquid chromatography. The NRAMP1 promoter polymorphism of 18 additional random controls was analyzed by microsatellite sizing. No allelism was found in NRAMP1 corresponding to the murine mutation, or in the two coding regions. In the NRAMP1 promoter microsatellite, 3 of 8 patients were heterozygous for a dinucleotide sequence insertion, as were 10 of 22 controls. None of the patients had either of the two known IFN-gammaR1 mutations. In conclusion, in women with MAI pulmonary disease, there is no evidence for a genetic defect in NRAMP1 or IFN-gammaR1 to correlate with disease.
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PMID:Analyses of the NRAMP1 and IFN-gammaR1 genes in women with Mycobacterium avium-intracellulare pulmonary disease. 947 46

I/St mice, previously characterized as susceptible to Mycobacterium tuberculosis H37Rv, were given 10(3) or 10(5) CFU intravenously. At two time points postinoculation, the cell suspensions that resulted from enzymatic digestion of lungs were enumerated and further characterized phenotypically and functionally. Regarding the T-cell populations recovered at 2 and 5 weeks postinfection, two main results were obtained: (i) the population of CD44(-) CD45RB+ cells disappeared within 2 weeks postinfection, while the number of CD44(+) CD45RB-/low cells slowly increased between weeks 2 and 5; (ii) when cocultured with irradiated syngeneic splenocytes, these lung T cells proliferated in the presence of H37Rv sonicate. Using H37Rv sonicate and irradiated syngeneic splenocytes to reactivate lung T cells, we selected five CD3(+) CD4(+) CD8(-) T-cell clones. In addition to the H37Rv sonicate, the five clones react to both a short-term culture filtrate and an affinity-purified 15- to 18-kDa mycobacterial molecule as assessed by the proliferative assay. However, there was a clear difference between T-cell clones with respect to cytokine (gamma interferon [IFN-gamma] and interleukin-4 [IL-4] and IL-10) profiles: besides one Th1-like (IFN-gamma+ IL-4(-)) clone and one Th0-like (IFN-gamma+ IL-4(+) IL-10(+)) clone, three clones produced predominantly IL-10, with only marginal or no IL-4 and IFN-gamma responses. Inhibition of mycobacterial growth by macrophages in the presence of T cells was studied in a coculture in vitro system. It was found that the capacity to enhance antimycobacterial activity of macrophages fully correlated with INF-gamma production by individual T-cell clones following genetically restricted recognition of infected macrophages. The possible functional significance of cytokine diversity among T-cell clones is discussed.
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PMID:An ex vivo study of T lymphocytes recovered from the lungs of I/St mice infected with and susceptible to Mycobacterium tuberculosis. 974 7

Interferon-alpha (IFN-alpha) is a cytokine exerting pleiotropic activities, including antimicrobial effects, especially directed against intracellular infectious bacteria. It may be administered by aerosol to reach the lower respiratory tract without systemic side effects. The aim of the study reported here was the evaluation of aerosolized IFN-alpha treatment (3 MU/dose, given three times a week; total study dose: 72 MU/2 mo) in combination with conventional antimycobacterial therapy in patients with pulmonary tuberculosis. Two groups of 10 patients each were compared before and after 2 mo of conventional antituberculous chemotherapy with or without inhaled IFN-alpha. Several biologic (bronchoalveolar lavage fluid [BALF] cellularity, Mycobacterium tuberculosis [MT] number in sputum), biochemical (BALF concentrations of 10 cytokines, BALF IFN-alpha receptor levels), and clinical (fever, vital signs, high-resolution computed tomography [HRCT] images) measures were made in these patients at the time of their enrollment and at the end of the observation period of the study. Fever, MT number in sputum, and abnormalities in HRCT images showed significantly earlier resolution in the IFN-alpha-treated group, together with a more significant decrease in BALF interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) concentrations and significantly greater pre- versus posttreatment variations in IL-2 and IFN-gamma. These data, taken together, suggest that IFN-alpha administration may favorably affect the evolution of pulmonary tuberculosis when combined with antimycobacterial therapy.
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PMID:Effects of aerosolized interferon-alpha in patients with pulmonary tuberculosis. 976 75


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