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Tuberculosis

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https://www.readbyqxmd.com/read/27856197/characterization-of-2-hydroxy-1-naphthaldehyde-isonicotinoyl-hydrazone-as-a-novel-inhibitor-of-methionine-aminopeptidases-from-mycobacterium-tuberculosis
#1
Sarah F John, Emmanuel Aniemeke, Ngan P Ha, Curtis R Chong, Peihua Gu, Jiangbing Zhou, Ying Zhang, Edward A Graviss, Jun O Liu, Omonike A Olaleye
Mycobacterium tuberculosis (Mtb) and the Human Immunodeficiency Virus (HIV) pose a major public health threat. The 2015 World Health Organization (WHO) report estimates that one in three HIV deaths is due to Mtb, the causative agent of Tuberculosis (TB). The lethal synergy between these two pathogens leads to a decline in the immune function of infected individuals as well as a rise in morbidity and mortality rates. The deadly interaction between TB and HIV, along with the heightened emergence of drug resistance, drug-drug interactions, reduced drug efficacy and increased drug toxicity, has made the therapeutic management of co-infected individuals a major challenge...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27745787/the-early-secreted-antigenic-target-of-6-kd-of-mycobacterium-tuberculosis-inhibits-the-proliferation-and-differentiation-of-human-peripheral-blood-cd34-cells
#2
Na Yi, Bock-Gie Jung, Xisheng Wang, RamaKrishna Vankayalapati, Buka Samten
Abnormalities in hematopoiesis are common in tuberculosis patients and highly prevalent in AIDS patients with tuberculosis coinfection. To explore the potential role of the early secreted antigenic target of 6-kD (ESAT-6) of Mycobacterium tuberculosis (Mtb) in abnormal hematopoiesis in tuberculosis, we studied the effect of ESAT-6 on proliferation and differentiation of in vitro-expanded CD34(+) cells isolated from the peripheral blood of the healthy donors. ESAT-6 but not control protein antigen 85A (Ag85A) of Mtb inhibited the proliferation of CD34(+) cell derived peripheral blood stem/progenitor cells (PBSPC) in a dose dependent manner when determined by MTT-assay...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27743706/cord-factor-as-an-invisibility-cloak-a-hypothesis-for-asymptomatic-tb-persistence
#3
Robert L Hunter, Shen-An Hwang, Chinnaswamy Jagannath, Jeffrey K Actor
Mycobacterium tuberculosis (MTB) has long been known to persist in grossly normal tissues even in people with active lesions and granulomas in other parts of the body. We recently reported that post-primary TB begins as an asymptomatic infection that slowly progresses, accumulating materials for a massive necrotizing reaction that results in cavitation. This paper explores the possible roles of trehalose 6,6' dimycolate (TDM) or cord factor in the ability of MTB to persist in such lesions without producing inflammation...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27743705/emerging-role-of-mesenchymal-stem-cells-during-tuberculosis-the-fifth-element-in-cell-mediated-immunity
#4
Arshad Khan, Robert L Hunter, Chinnaswamy Jagannath
Mesenchymal stem cells (MSCs) are non-hematopoietic cells that occur in almost all human tissues and can be cultured and expanded to large numbers in vitro. They secrete growth factors, cytokines, and chemokines and express Toll-like receptors on their surface, although multiple cell biological mechanisms remain unclear. MSCs are multi-potent and can differentiate into many cell types including adipocytes, neuronal cells and osteoclasts. Despite gaps in cell biology, because of their immunomodulatory and regenerative capacity, several hundred clinical trials have used MSCs for therapy of cancer, autoimmune diseases and control of inflammation during organ transplantation...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27742463/differentiating-between-live-and-dead-mycobacterium-smegmatis-using-autofluorescence
#5
Cynthia Wong, Ngan P Ha, Michal E Pawlowski, Edward A Graviss, Tomasz S Tkaczyk
While there have been research efforts to find faster and more efficient diagnostic techniques for tuberculosis (TB), it is equally important to monitor a patient's response to treatment over time, especially with the increasing prevalence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) TB. Between sputum smear microscopy, culture, and GeneXpert, only culture can verify viability of mycobacteria. However, it may take up to six weeks to grow Mycobacterium tuberculosis (Mtb), during which time the patient may have responded to treatment or the mycobacteria are still viable because the patient has MDR or XDR TB...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27742462/modulation-of-human-t-cell-cytokines-by-the-mycobacterium-tuberculosis-secreted-protein-wag31
#6
Buka Samten, Stewart Fannin, Krishna Sarva, Na Yi, Murty Madiraju, Malini Rajagopalan
Mycobacterium tuberculosis secretes a number of proteins into the extracellular milieu during growth. Several of these proteins have been associated with modulation of the host immune response. Antigen 84, or Wag31, is one such protein that is conserved among all mycobacterial species and is recognized by the sera from tuberculosis and leprosy patients. Here, we examined the effect of Wag31 on the ability of activated human T cells to produce cytokines such as IL-10, IL-17 and IFN-γ in response to combined anti-CD3 and anti-CD28 stimulation...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27742461/association-of-pellicle-growth-morphological-characteristics-and-clinical-presentation-of-mycobacterium-tuberculosis-isolates
#7
Ranjana Arora, Lisa Armitige, Audrey Wanger, Robert L Hunter, Shen-An Hwang
Trehalose 6,6'dimycolate (TDM) is a glycolipid found in nearly pure form on the surface of virulent Mycobacterium tuberculosis (MTB). This manuscript investigated the production of TDM, growth rate and colony morphology of multiple strains of MTB, each of which had been isolated from both pulmonary (sputum) and extrapulmonary sites of multiple patients. Since sputum contains MTB primarily from cavities and extrapulmonary biopsies are typically granulomas, this provided an opportunity to compare the behavior of single strains of MTB that had been isolated from cavities and granulomas...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27733245/differential-inflammasome-activation-signatures-following-intracellular-infection-of-human-macrophages-with-mycobacterium-bovis-bcg-or-trypanosoma-cruzi
#8
M B Huante, S Gupta, V C Calderon, S J Koo, M Sinha, B A Luxon, N J Garg, J J Endsley
Pathogens frequently exploit or evade inflammasome activation in order to survive and proliferate. Alternatively, inadequate inflammasome activation by attenuated microorganisms or adjuvanted subunit vaccines may contribute to poor longevity of protection. To further understand these pathways, we determined the differential inflammasome transcriptome of human THP monocyte-derived macrophages in response to Mycobacterium bovis BCG, as compared to LPS or Trypanosoma cruzi. The results identify the highly specific innate recognition programs associated with inflammasome activation by human macrophages exposed to these microbial stimuli...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27733244/tuberculosis-diabetes-epidemiology-in-the-border-and-non-border-regions-of-tamaulipas-mexico
#9
Bassent E Abdelbary, Moncerrato Garcia-Viveros, Horacio Ramirez-Oropesa, Mohammad H Rahbar, Blanca I Restrepo
Type 2 diabetes mellitus (DM) is a re-emerging risk factor for TB development and adverse TB outcomes. As a follow-up of our previous study in 1998-2004, we reassessed prevalence of DM and its associated factors among 8431 TB patients using surveillance data from 2006 to 2013 for the Mexican state of Tamaulipas, across the border with Texas. Prevalence of DM was 25.2%, with an increase of at least 2.8% over the study period. Newly discovered factors associated with TB-DM (versus no DM) were lower education and higher unemployment (p < 0...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27729258/new-directions-using-reporter-enzyme-fluorescence-ref-as-a-tuberculosis-diagnostic-platform
#10
Preeti Sule, Ronak Tilvawala, Parnia Behinaein, Grant K Walkup, Jeffrey D Cirillo
Although tuberculosis (TB) is one of the most common causes of morbidity and mortality in humans worldwide and diagnostic methods have been in place for more than 100 years, diagnosis remains a challenge. The main problems with diagnosis relate to the time needed to obtain a definitive result, difficulty in obtaining sputum, the primary clinical material used, and the ability of the causative agent, Mycobacterium tuberculosis, to cause disease in nearly any tissue within the body. In order to decrease incidence of TB, discovery of a novel interventions will be required, since current technologies have only been able to control numbers of infections, not reduce them...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27729257/sequencing-relative-to-hybridization-based-transcriptomics-approaches-better-define-mycobacterium-tuberculosis-stress-response-regulons
#11
Ashley V Veatch, Tianhua Niu, John Caskey, Amanda McGillivray, Uma Shankar Gautam, Ramesh Subramanian, K Gus Kousoulas, Smriti Mehra, Deepak Kaushal
Mycobacterium tuberculosis (Mtb) infections cause tuberculosis (TB), an infectious disease which causes ∼1.5 million deaths annually. The ability of this pathogen to evade, escape and encounter immune surveillance is fueled by its adaptability. Thus, Mtb induces a transition in its transcriptome in response to environmental changes. Global transcriptome profiling has been key to our understanding of how Mtb responds to the different stress conditions it faces during its life cycle. While this was initially achieved using microarray technology, RNAseq is now widely employed...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27729256/successful-management-of-acute-interstitial-nephritis-in-two-cases-of-disseminated-tuberculosis
#12
Quratulain Kizilbash
Acute interstitial nephritis (AIN) is characterized by an inflammatory infiltrate in the kidney interstitium and a decline in the creatinine clearance. Medications used for the treatment of tuberculosis have been implicated in the development of AIN, but there is limited data on how to manage AIN in this setting and which medications and dosages should be used to treat tuberculosis once AIN occurs. We describe two cases of AIN in the setting of disseminated tuberculosis in which AIN was successfully managed...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27727133/differential-positive-tspot-assay-responses-to-esat-6-and-cfp-10-in-health-care-workers
#13
Saroochi Agarwal, Duc T Nguyen, Justin D Lew, Larry D Teeter, Jose-Miguel Yamal, Blanca I Restrepo, Eric L Brown, Susan E Dorman, Edward A Graviss
BACKGROUND: The TSPOT.TB (TSPOT) diagnostic test for latent tuberculosis infection is based on a cell-mediated response to the Mycobacteria tuberculosis antigens, ESAT-6 and/or CFP-10, producing an "interferon-gamma footprint". We investigated the within-sample and within-subject variability of positive TSPOT assays due to the individual assay antigens' reactivity. METHODS: Positive TSPOT assay frequencies due to ESAT-6 or CFP-10 among health care workers (HCWs) at 6-month intervals for 18 months were compared...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27727132/comparing-tspot-assay-results-between-an-elispot-reader-and-manual-counts
#14
Saroochi Agarwal, Duc T Nguyen, Justin D Lew, Larry D Teeter, Jose-Miguel Yamal, Blanca I Restrepo, Eric L Brown, Susan E Dorman, Edward A Graviss
BACKGROUND: The interferon gamma release assay, TSPOT.TB (TSPOT) can be read by several methodologies, including an Elispot reader or manually by technician. We compared the results from these two counting methods. METHODS: Automated and manual TSPOT results among 2481 United States health care workers were compared. Cohen's kappa coefficient was used to determine the inter-rater agreement. Univariate and multiple logistic regression were used to investigate selected variable contributions...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27727131/culture-is-an-imperfect-and-heterogeneous-reference-standard-in-pediatric-tuberculosis
#15
Andrew R DiNardo, Anne Detjen, Pilar Ustero, Katherine Ngo, Jason Bacha, Anna M Mandalakas
BACKGROUND: In pediatric tuberculosis (pTB), culture is the accepted reference standard for assessing new diagnostic tests despite culture only confirming 10-50% of clinically diagnosed cases. METHODS: Using the studies previously included in the systematic review of Gene Xpert, we evaluated the diagnostic yield of culture. Children with symptoms and signs suggestive of TB were considered to have a clinical diagnosis if they were 1) culture positive or 2) followed clinically for at least one month and started on Anti-Tuberculosis Therapy (ATT)...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27727130/recombinant-human-lactoferrin-modulates-human-pbmc-derived-macrophage-responses-to-bcg-and-lps
#16
Shen-An Hwang, Marian L Kruzel, Jeffrey K Actor
Lactoferrin, an iron-binding glycoprotein found in mammalian mucosal secretions and granules of neutrophils, possesses several immune modulatory properties. Published reports indicate that lactoferrin enhances the efficacy of the tuberculosis vaccine, BCG (Bacillus Calmette Guerin), both by increasing macrophage and dendritic cell ability to stimulate receptive T cells and by modulating the inflammatory response. This report is the first to demonstrate the effects of a recombinant human lactoferrin (10 μg/mL) on human PBMC derived CD14(+) and CD16(+) macrophages stimulated with a strong (LPS, 10 ng/mL) or weaker (BCG, MOI 1:1) stimulator of inflammation...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27727129/recombinant-bacillus-subtilis-spores-for-the-delivery-of-mycobacterium-tuberculosis-ag85b-cfp10-secretory-antigens
#17
Kishore Das, Tima Thomas, Omar Garnica, Subramanian Dhandayuthapani
Tuberculosis continues to be a great cause of morbidity and mortality in different parts of the world. Unfortunately, the current BCG vaccine being administered is not fully protective against tuberculosis; therefore, there is a great need for alternate vaccines. With an aim to develop such vaccines, we have analyzed the utility of Bacillus subtilis spores for the expression of two major immunodominant antigens of Mycobacterium tuberculosis, Ag85B and CFP10. We created three recombinant B. subtilis strains to express a truncated fusion of Ag85B191-325 and CFP101-70 antigens (T85BCFP), either on the spore coat (MTAG1 strain) or in the cytosol of B...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27720379/texas-tuberculosis-research-symposium-2016-research-and-clinical-collaboration-within-the-state-of-texas-towards-elimination-of-tb
#18
Edward A Graviss, Jeffrey K Actor
No abstract text is available yet for this article.
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27720378/metformin-candidate-host-directed-therapy-for-tuberculosis-in-diabetes-and-non-diabetes-patients
#19
Blanca I Restrepo
Despite major advances in tuberculosis (TB) control, TB continues to be a leading cause of death worldwide. The discovery of new anti-TB treatment drugs and regimens that target drug-sensitive and drug-resistant TB are being complemented with a search for adjunct host-directed therapies that synergize for Mycobacterium tuberculosis (Mtb) elimination. The goal of host-directed therapies is to boost immune mechanisms that diminish excess inflammation to reduce lung tissue damage and limit Mtb growth. Metformin is the most commonly-used medication for type 2 diabetes, and a candidate for host-directed therapy for TB...
September 28, 2016: Tuberculosis
https://www.readbyqxmd.com/read/27720377/predictive-value-of-serum-bradykinin-and-desarg-9-bradykinin-levels-for-chemotherapeutic-responses-in-active-tuberculosis-patients-a-retrospective-case-series
#20
Xu Qian, Duc T M Nguyen, Yaojun Li, Jianxin Lyu, Edward A Graviss, Tony Y Hu
BACKGROUND: There is an urgent need for methods that can rapidly and accurately assess therapeutic responses in patients with active tuberculosis (TB) in order to predict treatment outcomes. Exposure to bacterial pathogens can rapidly activate the plasma contact system, triggering the release of bradykinin (BK) and its metabolite desArg(9)-bradykinin (DABK) to induce inflammation and innate immune responses. We hypothesized that serum BK and DABK levels might act as sensitive immune response signatures for changes in Mycobacterium tuberculosis (Mtb) burden, and therefore examined how serum levels of these markers corresponded with anti-TB therapy in a small cohort of active TB cases...
September 28, 2016: Tuberculosis
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