42 research outputs found

    Cardiac magnetic resonance in tropical endomyocardial fibrosis

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    Background: Endomyocardial fibrosis has varied presentatation and difficult to diagnose. Aim to elucidate the role of Cardiac Magnetic Resonance (CMR) imaging in the evaluation of Endomyocardial Fibrosis (EMF) and to devise diagnostic criteria for the disease.Methods: Retrospective analysis of cases of restrictive cardiomyopathy referred for Magnetic resonance imaging over a period of 5 years. All patients underwent 1.5 T CMR imaging (Magnetom Avanto, Siemens, Germany) with standard cardiomyopathy protocol. Criteria for diagnosis of RCM included normal sized ventricles, normal/reduced systolic function, uni-/bi-atrial enlargement, normal pericardium and absent septal bounce. Cases diagnosed as EMF on CMR were included in this study. Statistical analysis performed using SPSS software.Results: EMF was diagnosed in 20 patients (31%) [12 males; age 39±18 years]. Ten patients had Right Centricular (RV) EMF, 3 had Left Ventricular (LV) EMF, while 7 had bi-ventricular EMF. Oedema indicating ongoing inflammation was seen in 4 (20%) cases. Apical thrombus was seen in 8(40%) cases and was present in 35% cases of RV and 20% cases of LV involvement. Subendocardial delayed enhancement was always present in the involved ventricle. The RV apex was obliterated in 100% of patients with RV EMF, while LV apex was similarly obliterated in 66% cases with LV disease. Mild-moderate pericardial effusion was observed in 8 patients. On the basis of CMR findings, the disease was classified as early necrotic phase in 1, thrombotic necrotic in 4 and late fibrotic phase in 13 and of different stages in ventricles in 2 cases.Conclusions: EMF was the commonest cause of RCM in this series. Major diagnostic criteria of EMF on CMR include subendocardial delayed enhancement and apical obliteration. Oedema and thrombus are variable findings, depending on disease severity

    Dormant Mycobacterium tuberculosis converts isoniazid to the active drug in a Wayne’s model of dormancy

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    Isoniazid (INH) is one among the four first-line drugs used in the treatment of tuberculosis. The bactericidal activity of INH is due to its ability to inhibit mycolic acid synthesis, which is an integral component of the mycobacterial cell wall. Non-replicating Mycobacterium tuberculosis (MTB) is phenotypically resistant to INH. The exact mechanism of this resistance is not clear, although the inability of dormant MTB to convert the pro-drug into an active form is thought to be one of the possible reasons. Employing targeted metabolomics approach, we show that dormant MTB can metabolize INH into its active INH-NAD+ adduct form. Further we show that the dormant bacteria have unaltered gene expression levels of katG and inhA (INH metabolizing enzymes). Transcript levels of drug efflux pump proteins which were low during dormancy did not increase in response to INH treatment. These findings point to an alternative mechanism for INH resistance in dormant MTB, which needs to be further elucidated

    Hypothetical protein Rv3423.1 of Mycobacterium tuberculosis is a histone acetyltransferase

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    We isolated an 8 kDa mycobacterial hypothetical protein, Rv3423.1, from the chromatin of human macrophages infected with Mycobacterium tuberculosis H37Rv. Bioinformatics predictions followed by in vitro biochemical assays with purified recombinant protein showed that Rv3423.1 is a novel histone acetyltransferase that acetylates histone H3 at the K9/K14 positions. Transient transfection of macrophages containing GFP-tagged histone H1 with RFP-tagged Rv3423.1 revealed that the protein co-localizes with the chromatin in the nucleus. Co-immunoprecipitation assays confirmed that the Rv3423.1-histone interaction is specific. Rv3423.1 protein was detected in the culture filtrate of virulent but not avirulent M. tuberculosis. Infection of macrophages with recombinant Mycobacterium smegmatis constitutively expressing Rv3423.1 resulted in a significant increase in the number of intracellular bacteria. However, the protein did not seem to offer any growth advantage to free-living recombinant M. smegmatis. It is highly likely that, by binding to the host chromatin, this histone acetyltransferase from M. tuberculosis may manipulate the expression of host genes involved in anti-inflammatory responses to evade clearance and to survive in the intracellular environment

    Rv0474 is a copper-responsive transcriptional regulator that negatively regulates expression of RNA polymerase subunit in Mycobacterium tuberculosis

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    We characterize Rv0474, a putative transcriptional regulatory protein of Mycobacterium tuberculosis, which is found to function as a copper-responsive transcriptional regulator at toxic levels of copper. It is an autorepressor, but at elevated levels (10-250 m) of copper ions the repression is relieved resulting in an increase in Rv0474 expression. Copper-bound Rv0474 is recruited to the rpoB promoter leading to its repression resulting in the growth arrest of the bacterium. Mutational analysis showed that the helix-turn-helix and leucine zipper domains of Rv0474 are essential for its binding to Rv0474 and rpoB promoters, respectively. The mechanism of Rv0474-mediated rpoB regulation seems to be operational only in pathogenic mycobacteria that can persist inside the host
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