Fluctuating Behavior and Influential Factors in the Performance of the QuantiFERON-TB Gold In-Tube Assay in the Diagnosis of Tuberculosis.

Background: The QuantiFERON-TB Gold In-Tube (QFT-GIT) is a newly developed but widely used interferon-γ release assay for diagnosing tuberculosis (TB). However, research has not determined whether age or the use of an immune suppressive or anti-TB treatment influences this assay's ability to detect TB. We assessed the QFT-GIT diagnostic performance for active tuberculosis (ATB) in children and adults in an endemic country and explored the effects of glucocorticoids and anti-TB therapy on the diagnostic value of the QFT-GIT.

Evolution and transmission patterns of extensively drug-resistant tuberculosis in China.

The emergence and transmission of extensively drug-resistant tuberculosis (XDR-TB) pose an increasing threat to global TB control. This study aimed to identify the patterns of evolution and transmission dynamics of XDR-TB in populations in a region of China where TB is highly endemic. We analyzed a total of 95 XDR-TB isolates collected from 2003 to 2009 in Chongqing, China.

Influencial factors of the performance of interferon-γ release assays in the diagnosis of childhood tuberculosis.

Diagnosis of active tuberculosis (TB) in children remains difficult. This study aimed at evaluating the ability of interferon-gamma release assays (IGRAs) in the detection of active TB in human immunodeficiency virus-negative children vaccinated with Bacille Calmette-Guérin and investigating the effect of prednisolone treatment on the IGRAs performance. Among the 162 children with suspected TB disease recruited in China, 60 were tested with QuantiFERON-TB Gold In Tube (QFT-GIT) and 102 were tested with T-SPOT.

Evaluation of the diagnostic potential of IP-10 and IL-2 as biomarkers for the diagnosis of active and latent tuberculosis in a BCG-vaccinated population.

Background: The Mycobacterium tuberculosis (Mtb)-specific T-cell interferon gamma release assays (IGRAs) are useful in detecting Mtb infection but perform poorly at distinguishing active tuberculosis disease (ATB) and latent tuberculosis infection (LTBI). This study is aimed at evaluating additional cytokines as biomarkers besides interferon-gamma (IFN-γ) to improve the identification of ATB and LTBI.

Methodology/principal Findings: Sixty-six patients with ATB, 73 household contacts (HHC) of ATB patients and 76 healthy controls (HC) were recruited to undergo QuantiFERON TB GOLD in-tube assay (QFT) and the enzyme-linked immunosorbent assay (ELISA) where the release of IFN-γ, IFN-γ inducible protein 10 (IP-10), Interleukin 2 (IL-2) and Tumor Necrosis Factor-α (TNF-α) was determined in the whole blood with or without antigen-stimulation.

Underestimation of the resistance of Mycobacterium tuberculosis to second-line drugs by the new GenoType MTBDRsl test.

The GenoType MTBDRsl is a new-generation PCR-based line-probe assay for the detection of extensively drug-resistant tuberculosis (XDR-TB). This study evaluated the performance of MTBDRsl in detecting genotypic resistance to ethambutol, kanamycin, and ofloxacin in Mycobacterium tuberculosis (MTB) strains. The drug resistance of 262 unique clinical MTB isolates from China was analyzed with MTBDRsl, traditional TB drug susceptibility testing (DST), and sequencing.

Mycobacterium tuberculosis region of difference (RD) 2 antigen Rv1985c and RD11 antigen Rv3425 have the promising potential to distinguish patients with active tuberculosis from M. bovis BCG-vaccinated individuals.

Antigens encoded in the region of difference (RD) of Mycobacterium tuberculosis constitute a potential source of specific immunodiagnostic antigens for distinguishing tuberculosis (TB) infection from BCG vaccination. We evaluated the diagnostic potential of specific T-cell epitopes selected from two immunodominant antigens, Rv1985c and Rv3425, from RD2 and RD11, respectively, on the basis of epitope mapping, in TB patients and BCG-vaccinated healthy individuals. Using a whole-blood gamma interferon release assay, a wide array of epitopes was recognized on both Rv1985c and Rv3425 in TB patients.

Interferon-gamma release assay performance in pulmonary and extrapulmonary tuberculosis.

Background: The diagnosis of tuberculosis remains difficult. This study aimed to assess performance of interferon-gamma release assay (IGRA) in diagnosis of active tuberculosis (ATB) with pulmonary and extrapulmonary involvements, and to determine the diagnostic role of IGRA (T-SPOT.TB) and tuberculin skin test (TST) in BCG-vaccinated population.

Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: a preliminary study.

To explore biologic behaviors and disease relevance of microRNAs (miRNAs) in the development of active tuberculosis (ATB), we investigated the expression profile of Mycobacterium tuberculosis (MTB) purified protein derivative (PPD)-induced miRNAs to determine the specific miRNAs involved in the pathogenesis of ATB. The expression profile of miRNA under PPD challenge was first measured using microarray analysis in peripheral blood mononuclear cells isolated from ATB patients and healthy controls (HC). The remarkably reactive miRNAs were then validated in a larger cohort by quantitative real-time polymerase chain reaction (qRT-PCR).

Novel biomarkers distinguishing active tuberculosis from latent infection identified by gene expression profile of peripheral blood mononuclear cells.

Background: Humans infected with Mycobacterium tuberculosis (MTB) can delete the pathogen or otherwise become latent infection or active disease. However, the factors influencing the pathogen clearance and disease progression from latent infection are poorly understood. This study attempted to use a genome-wide transcriptome approach to identify immune factors associated with MTB infection and novel biomarkers that can distinguish active disease from latent infection.

E3 ubiquitin ligase Siah-1 facilitates poly-ubiquitylation and proteasomal degradation of the hepatitis B viral X protein.

Hepatitis B viral X protein (HBx) is a multifunctional transactivator and implicated in hepatitis B virus (HBV) replication and hepatocarcinogenesis. HBx can be ubiquitinated and degraded through ubiquitin-proteasome pathway. However, the E3 ubiquitin ligase regulating HBx ubiquitin-dependent degradation is still unknown.

Nonuniform activation and the mechanics of myocardial trabeculae with fast or slow myosin.

Left ventricular (LV) wall motion abnormalities reflect regional nonuniform contraction which may be arrhythmogenic. We studied sarcomere mechanics and force development (F) in uniform and nonuniform trabeculae using a model in which half of the muscle can be rendered weak by exposure to low [Ca2+]o. Stretch allowed the weak muscle segment to generate a force that was four-fold higher than force when the whole muscle was exposed to low [Ca2+]o.

Effects of therapy using the Celacade system on structural and functional cardiac remodelling in rats following myocardial infarction.

Background: Immune modulation by the Celacade system (Vasogen Inc, Canada) decreases mortality and hospitalization in human heart failure.

Objectives: To study the effects of Celacade in rats on acute cytokine expression after coronary artery ligation, cardiac dimensions following myocardial infarction (MI), and systolic and diastolic function of cardiac muscle in MI.

Methods: Celacade treatment was administered 14 days before coronary artery ligation and monthly after the surgery.

Residue Gln4863 within a predicted transmembrane sequence of the Ca2+ release channel (ryanodine receptor) is critical for ryanodine interaction.

Despite the pivotal role of ryanodine in ryanodine receptor (RyR) research, the molecular basis of ryanodine-RyR interaction remains largely undefined. We investigated the role of the proposed transmembrane helix TM10 in ryanodine interaction and channel function. Each amino acid residue within the TM10 sequence, 4844IIFDITFFFFVIVILLAIIQGLII4867, of the mouse RyR2 was mutated to either alanine or glycine.