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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The footpad reaction to autoclaved whole Mycobacterium lepraemurium organisms (MLM lepromin) in high-resistance (C57BL) and low-resistance (BALB/c) mice was studied. Infected C57BL mice gave a prolonged footpad response persisting for 4 weeks after skin testing with high and low doses of lepromin. This was accompanied by mononuclear cell infiltration. Uninfected C57BL mice gave no response. The majority of infected BALB/c mice gave no increase in footpad thickness. However, a high proportion of infected and control BALB/c mice tested with the high dose showed mononuclear cell infiltration which resembled that in C57BL mice. The low dose caused little infiltration in infected or control BALB/c mice. The course of infection in the two strains was different. Dissemination of organisms from the infected footpad was minimal in C57BL mice 5 months after infection. In BALB/c mice, dissemination to the draining lymph node and to some extent to the liver had occurred by 5 months. The draining lymph node of BALB/c mice showed histological evidence of local antibody formation, which uas not found in C57BL mice. On the basis of these findings, it was possible to fit murine leprosy in these two strains into a classification similar to that used for human leprosy.
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PMID:Mitsuda-type lepromin reactions as a measure of host resistance in Mycobacterium lepraemurium infection. 37 56

The kinetics of cell-mediated immunity developed during the course of Mycobacterium lepraemurium infection were determined in resistant (C57BL) and susceptible (BALB/c) mice. Control of M. lepraemurium growth following footpad infection was T-cell dependent in C57BL mice as shown by the finding that T-cell deprived mice had enhanced bacterial counts in the footpad. In contrast, T-cell deprivation did not significantly alter the course of infection in BALB/c mice. However a T-cell dependent inflammatory response, resulting in an increase in size of the infected footpad, occurred in both strains, although it developed slightly later in BALB/c mice. Cells isolated from the lymph nodes, draining the infected foot-pads, were assayed for their proliferative responses to heat-killed M. lepraemurium (HK-MLM) antigens. Although lymph node cells from both mouse strains proliferated to HK-MLM early in the infection (1-2 weeks) both C57BL and BALB/c mice developed diminished in vitro proliferative reactivity within 4-6 weeks post-infection. Supernatants derived from cultures of lymph-node cells that had been stimulated with concanavalin A (Con A) or HK-MLM antigens, were assayed for the presence of macrophage-activating factor (MAF) activity using a tumour cytostasis assay and interferon (IFN) activity using a viral growth inhibition assay. Significantly higher levels of MAF and IFN were found in culture supernatants deprived from HK-MLM stimulated lymph-node cells from infected C57BL mice than from BALB/c mice during the first 8 weeks of infection. However, cells from infected mice of both strains produced similar amounts of both MAF and IFN in response to Con A.
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PMID:Resistance to Mycobacterium lepraemurium is correlated with the capacity to generate macrophage activating factor(s) in response to mycobacterial antigens in vitro. 243 95

Infection of mice with Mycobacterium lepraemurium caused significant functional alterations of the mononuclear phagocyte system. Accelerated clearance of sheep red blood cells was consistently demonstrated throughout the infection and the infected mice showed progressive anaemia. Infected mice showed an enhanced ability to limit growth of phagocytosed Listeria monocytogenes in spleens during the early stages of infection, whereas moribund leprous mice lost this ability. Autoradiography showed that uninfected Kupffer cells and splenic macrophages of moribund mice could still phagocytose Listeria, suggesting that MLM infection did not affect the capacity of Listeria to localize to macrophages but interfered in some way with subsequent killing of such bacteria. The possible mechanisms underlying these observations are discussed.
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PMID:Evaluation of phagocytic function in Mycobacterium lepraemurium infection. 309 Jan 12

Antigen-specific and mitogen-nonspecific T-lymphocyte proliferation and lymphokine release (interleukin 2 and macrophage activation factor) were studied in BALB/c and CBA mice infected intravenously with 10(8) Mycobacterium lepraemurium organisms. The responsiveness of spleen cells from infected animals to Con A and specific MLM antigen declined as the infection progressed. Thus, the decreased responsiveness appeared earlier and was more profound in the relatively susceptible BALB/c strain than in the relatively resistant CBA strain. Nylon-wool-purified, T-cell-enriched spleen cells from both strains, however, responded to both M. lepraemurium antigen and Con A until the later stages of infection (17 weeks postinfection). The relevance of nonspecific immunodepression mediated by nylon-wool-adherent spleen cells to the progressive nature of this infection is discussed.
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PMID:T-cell responsiveness in Mycobacterium lepraemurium infections in a "resistant" (CBA) and a "susceptible" (BALB/c) mouse strain. 638 89

C3H mice were immunized subcutaneously with water soluble antigens of ultrasonicated Mycobacterium lepraemurium bacilli (MLMSon-S) in Freund's incomplete adjuvant (FIA) and challenged with 1 X 10(6)-1.25 X 10(8) live MLM bacilli inoculated into the foot pad. No swelling of the infected foot pad and no differences in bacillary multiplication and dissemination between the immunized mice and the control animals were observed in the first nine weeks. From nine weeks on, a small foot pad swelling developed in the immunized mice. Twenty weeks after inoculation, the number of bacilli in the foot pad, the popliteal lymph node, and the spleen was significantly lower in the immunized mice than in the normal controls after challenge with the lowest bacillary doses. Cyclophosphamide (CY) pretreatment did not increase the effect of immunization. The addition of MLM cell wall fragments to the emulsion used for immunization tended to increase the difference between immunized and normal animals, while no further increase of the immunization effect was obtained by the use of Freund's complete adjuvant (FCA). A tendency toward a plateau phenomenon for the multiplication of MLM bacilli was observed in the normal mice. In nonimmunized mice, CY treatment caused some reduction in bacillary numbers in the foot pads, and reinfection experiments suggested that a small reduction in susceptibility had been induced by the priming infection. Although unable to prevent a progressive course of the infection, genetically low-resistant C3H mice were able to modify the development of the infection by mechanisms that were activated by the infection itself. Similar mechanisms were facilitated by immunization with MLMSon-S.
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PMID:Immunization of highly susceptible C3H mice with ultrasonicated Mycobacterium lepraemurium (MLM) bacilli facilitates the development of increased resistance during MLM infection. 654 Dec 3

The renewed urgency to develop new treatments for Mycobacterium tuberculosis (Mtb) infection has resulted in large-scale phenotypic screening and thousands of new active compounds in vitro. The next challenge is to identify candidates to pursue in a mouse in vivo efficacy model as a step to predicting clinical efficacy. We previously analyzed over 70 years of this mouse in vivo efficacy data, which we used to generate and validate machine learning models. Curation of 60 additional small molecules with in vivo data published in 2014 and 2015 was undertaken to further test these models. This represents a much larger test set than for the previous models. Several computational approaches have now been applied to analyze these molecules and compare their molecular properties beyond those attempted previously. Our previous machine learning models have been updated, and a novel aspect has been added in the form of mouse liver microsomal half-life (MLM t1/2) and in vitro-based Mtb models incorporating cytotoxicity data that were used to predict in vivo activity for comparison. Our best Mtb in vivo models possess fivefold ROC values > 0.7, sensitivity > 80%, and concordance > 60%, while the best specificity value is >40%. Use of an MLM t1/2 Bayesian model affords comparable results for scoring the 60 compounds tested. Combining MLM stability and in vitro Mtb models in a novel consensus workflow in the best cases has a positive predicted value (hit rate) > 77%. Our results indicate that Bayesian models constructed with literature in vivo Mtb data generated by different laboratories in various mouse models can have predictive value and may be used alongside MLM t1/2 and in vitro-based Mtb models to assist in selecting antitubercular compounds with desirable in vivo efficacy. We demonstrate for the first time that consensus models of any kind can be used to predict in vivo activity for Mtb. In addition, we describe a new clustering method for data visualization and apply this to the in vivo training and test data, ultimately making the method accessible in a mobile app.
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PMID:Machine Learning Model Analysis and Data Visualization with Small Molecules Tested in a Mouse Model of Mycobacterium tuberculosis Infection (2014-2015). 2733 15