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https://www.readbyqxmd.com/read/28636589/identifying-specificity-groups-in-the-t-cell-receptor-repertoire
#1
Jacob Glanville, Huang Huang, Allison Nau, Olivia Hatton, Lisa E Wagar, Florian Rubelt, Xuhuai Ji, Arnold Han, Sheri M Krams, Christina Pettus, Nikhil Haas, Cecilia S Lindestam Arlehamn, Alessandro Sette, Scott D Boyd, Thomas J Scriba, Olivia M Martinez, Mark M Davis
T cell receptor (TCR) sequences are very diverse, with many more possible sequence combinations than T cells in any one individual. Here we define the minimal requirements for TCR antigen specificity, through an analysis of TCR sequences using a panel of peptide and major histocompatibility complex (pMHC)-tetramer-sorted cells and structural data. From this analysis we developed an algorithm that we term GLIPH (grouping of lymphocyte interactions by paratope hotspots) to cluster TCRs with a high probability of sharing specificity owing to both conserved motifs and global similarity of complementarity-determining region 3 (CDR3) sequences...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28635184/design-synthesis-and-biological-evaluation-of-isothiosemicarbazones-with-antimycobacterial-activity
#2
Eva Novotná, Karel Waisser, Jiří Kuneš, Karel Palát, Lenka Skálová, Barbora Szotáková, Vladimír Buchta, Jiřina Stolaříková, Vít Ulmann, Marcela Pávová, Jan Weber, Jitka Komrsková, Pavlína Hašková, Ivan Vokřál, Vladimír Wsól
A series of benzaldehyde and salicylaldehyde-S-benzylisothiosemicarbazones was synthesized and tested against 12 different strains of mycobacteria, Gram-positive and Gram-negative bacteria, and the significant selectivity toward mycobacteria was proved. Twenty-eight derivatives were evaluated for the inhibition of isocitrate lyase, which is a key enzyme of the glyoxylate cycle necessary for latent tuberculosis infection, and their iron-chelating properties were investigated. Two derivatives, 5-bromosalicylaldehyde-S-(4-fluorobenzyl)-isothiosemicarbazone and salicylaldehyde-S-(4-bromobenzyl)-isothiosemicarbazone, influenced the isocitrate lyase activity and caused a better inhibition at 10 μmol/L than 3-nitropropionic acid, a standard inhibitor...
June 21, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28628015/latent-tuberculosis-potential-biomarkers-reactivation-of-infection
#3
I Pantsulaia, N Kikodze, T Chikovani
Tuberculosis continues to be one of the most important infectious causes of death worldwide. Despite substantial investments and progress made in expansion of directly observed therapy short course (DOTS) strategy, improved treatment completion rates and inadequate case detection remains a major obstacle for global control of Tuberculosis. The global case detection rate has increased from 28% to 60%. However, it is estimated that approximately 50% of patients with tuberculosis are still not diagnosed or treated appropriately...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28625141/bedaquiline-a-new-hope-for-shorter-and-better-anti-tuberculosis-regimens
#4
Niccolò Riccardi, Filippo Del Puente, Federica Magnè, Lucia Taramasso, Antonio Di Biagio
In 2014, an estimated 1.8 million people died from Mycobacterium tuberculosis (MTB); moreover, 680,000 people developed multidrug-resistant TB (MDR-TB). Currently available anti-MDR and XDR regimens are long-lasting and expensive, need high adherence and are undermined by a high frequency of adverse drug events, thus leading to a low success rate; moreover, in the last 50 years only two new molecules, bedaquiline (BDQ) and delamanid, have been approved and released for treatment of MDR-TB. BDQ is a diarylquinoline anti-mycobacterial drug, active regardless the state of MTB; in fact, its efficacy is conserved against replicating and non-replicating bacilli, despite extracellular or intracellular location...
June 19, 2017: Recent Patents on Anti-infective Drug Discovery
https://www.readbyqxmd.com/read/28622258/tuberculosis-still-an-emerging-threat
#5
Carol Johnson, K Alexis Moore, Jacqueline Patterson-Johnson
Primary care providers must be aggressive in their assessment and screening of tuberculosis (TB) infection, which is still a major cause of mortality and morbidity worldwide. This article highlights the overall management of TB infection including the appropriate screening, diagnosis, and treatment of both latent and active infection.
July 15, 2017: Nurse Practitioner
https://www.readbyqxmd.com/read/28620394/vitamin-d-counteracts-mycobacterium-tuberculosis-induced-cathelicidin-downregulation-in-dendritic-cells-and-allows-th1-differentiation-and-ifn%C3%AE-secretion
#6
Anna K O Rode, Martin Kongsbak, Marie M Hansen, Daniel Villalba Lopez, Trine B Levring, Anders Woetmann, Niels Ødum, Charlotte M Bonefeld, Carsten Geisler
Tuberculosis (TB) presents a serious health problem with approximately one-third of the world's population infected with Mycobacterium tuberculosis in a latent state. Experience from the pre-antibiotic era and more recent clinical studies have established a beneficial role of sunlight and vitamin D in patients with TB. At the same time, experimental data have shown that Th1 cells through production of IFNγ are crucial for cathelicidin release by macrophages, bacterial killing, and containment of M. tuberculosis in granulomas...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28610785/chemokines-additional-to-ifn-%C3%AE-can-be-used-to-differentiate-among-mycobacterium-tuberculosis-infection-possibilities-and-provide-evidence-of-an-early-clearance-phenotype
#7
Ditthawat Nonghanphithak, Wipa Reechaipichitkul, Wises Namwat, Vivek Naranbhai, Kiatichai Faksri
Current diagnostic tests for tuberculosis (TB) remain limited in their ability to discriminate between active TB (ATB) and latent TB infection (LTBI). Early clearance (EC) of TB by individuals exposed to Mycobacterium tuberculosis is a debated phenomenon for which evidence is lacking. We measured and compared secreted chemokines in the plasma fraction from 48 ATB, 38 LTBI, 162 presumed EC and 39 healthy controls (HC) using the QuantiFERON(®)-TB Gold In-Tube assay. Single chemokine markers were limited in their ability to discriminate between ATB and LTBI: IFN-γ showed 16...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28605520/serial-tuberculosis-screening-in-inflammatory-bowel-disease-patients-under-anti-tnf%C3%AE-therapy
#8
Cândida Abreu, Joana Afonso, Cláudia Camila Dias, Rogério Ruas, António Sarmento, Fernando Magro
Background and aims: One of the adverse effects of the tumour necrosis factor-α monoclonal antibodies for the treatment of immune-mediated inflammatory diseases is a higher propensity for tuberculosis development. The aim of this study was to explore the utility and sensitivity of serial tuberculosis screening during anti-TNFα treatment. Methods: A cohort of 46 inflammatory bowel disease patients on infliximab was prospectively recruited and followed for 26 months...
June 9, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28604316/when-students-become-patients-tb-disease-among-medical-undergraduates-in-cape-town-south-africa
#9
Helene-Mari Van der Westhuizen, Angela Dramowski
BACKGROUND: Medical students acquire latent tuberculosis (TB) infection at a rate of 23 cases/100 person-years. The frequency and impact of occupational TB disease in this population are unknown. METHODS: A self-administered questionnaire was distributed via email and social media to current medical students and recently graduated doctors (2010 - 2015) at two medical schools in Cape Town. Individuals who had developed TB disease as undergraduate students were eligible to participate...
May 24, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28602386/respiratory-infections-associated-with-anti-tnf%C3%AE-agents
#10
REVIEW
E Blanchard, M-E Truchetet, I Machelart, J Séneschal, C Raherison-Semjen
Anti-TNFα agents have proved effective in the treatment of various inflammatory, rheumatologic, dermatologic, and gastrointestinal diseases. Severe respiratory tract infections of bacterial or fungal origin have emerged as important complications in patients receiving such treatments. The risk of infection due to anti-TNFα therapy is difficult to assess in these patients who are immunocompromised because of the underlying disease itself and of previous or concomitant immunosuppressive drugs. This excessive infection risk seems real, particularly in the first six months following treatment initiation, and higher for patients receiving anti-TNFα monoclonal antibodies than for those receiving soluble TNFα receptor...
June 8, 2017: Médecine et Maladies Infectieuses
https://www.readbyqxmd.com/read/28601524/rifampin-stability-and-solution-concentration-enhancement-through-amorphous-solid-dispersion-in-cellulose-%C3%AF-carboxyalkanoate-matrices
#11
Hale Çiğdem Arca, Laura I Mosquera-Giraldo, Junia M Pereira, Nammalwar Sriranganathan, Lynne S Taylor, Kevin J Edgar
Tuberculosis (TB) is a deadly infectious disease; approximately 2 billion people are currently latently infected with the causative agent Mycobacterium tuberculosis. Approximately 8 million new active cases and 2 million deaths due to TB are recorded annually(1). Rifampin (Rif) is a vital first line TB treatment drug. Its effectiveness is hampered by the high dose required (600 mg 1x/day) and by its moderate, variable bioavailability. These issues can be explained by Rif instability at gastric pH, limited solubility at neutral pH, polymorphism, and stimulation of its own metabolism...
June 7, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28598206/a-novel-in-vitro-human-granuloma-model-of-sarcoidosis-and-latent-tb-infection
#12
Elliott D Crouser, Peter White, Evelyn Guirado Caceres, Mark W Julian, Audrey C Papp, Landon W Locke, Wolfgang Sadee, Larry S Schlesinger
Many aspects of pathogenic granuloma formation are poorly understood requiring new relevant laboratory models that represent the complexity (genetics and diversity) of human disease. To address this need, we developed an in vitro model of granuloma formation using human peripheral blood mononuclear cells (PBMCs) derived from patients with active sarcoidosis, latent tuberculosis (TB) infection (LTBI), or normal healthy controls. PBMCs were incubated for 7 days with uncoated polystyrene beads or beads coated with purified protein derivative (PPD) or human serum albumin (HSA)...
June 9, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28597820/oxidative-phosphorylation-as-a-target-space-for-tuberculosis-success-caution-and-future-directions
#13
Gregory M Cook, Kiel Hards, Elyse Dunn, Adam Heikal, Yoshio Nakatani, Chris Greening, Dean C Crick, Fabio L Fontes, Kevin Pethe, Erik Hasenoehrl, Michael Berney
The emergence and spread of drug-resistant pathogens, and our inability to develop new antimicrobials to combat resistance, have inspired scientists to seek out new targets for drug development. The Mycobacterium tuberculosis complex is a group of obligately aerobic bacteria that have specialized for inhabiting a wide range of intracellular and extracellular environments. Two fundamental features in this adaptation are the flexible utilization of energy sources and continued metabolism in the absence of growth...
June 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28595594/prevalence-and-risk-factors-for-latent-tuberculosis-infection-among-healthcare-workers-in-nampula-central-hospital-mozambique
#14
Celso Belo, Saloshni Naidoo
BACKGROUND: Healthcare workers in high tuberculosis burdened countries are occupationally exposed to the tuberculosis disease with uncomplicated and complicated tuberculosis on the increase among them. Most of them acquire Mycobacterium tuberculosis but do not progress to the active disease - latent tuberculosis infection. The objective of this study was to assess the prevalence and risk factors associated with latent tuberculosis infection among healthcare workers in Nampula Central Hospital, Mozambique...
June 8, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28589321/latent-tuberculosis-infection-and-tuberculosis-in-patients-with-rheumatic-diseases-treated-with-anti-tumor-necrosis-factor-agents
#15
Giovana Garziera, André Luis Bittencourt Morsch, Felipe Otesbelgue, Fernanda Luiza Staub, Penélope Esther Palominos, Claiton Viegas Brenol, Denise Rossato Silva
The introduction of biological agents, especially the tumor necrosis factor inhibitors (anti-TNF), for the treatment of rheumatic diseases increased the risk of developing tuberculosis (TB). Screening for latent TB infection (LTBI) is strongly recommended before starting therapy with anti-TNF agents. The objective of this study was to identify the prevalence of LTBI and TB among patients with rheumatic diseases on anti-TNF agents. This is a cross-sectional study. The electronic medical records of all adult patients (≥18 years old) undergoing anti-TNF treatment were reviewed...
June 6, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28587792/breaking-fat-how-mycobacteria-and-other-intracellular-pathogens-manipulate-host-lipid-droplets
#16
REVIEW
Caroline Barisch, Thierry Soldati
Tuberculosis (Tb) is a lung infection caused by Mycobacterium tuberculosis (Mtb). With one third of the world population latently infected, it represents the most prevalent bacterial infectious diseases worldwide. Typically, persistence is linked to so-called "dormant" slow-growing bacteria, which have a low metabolic rate and a reduced response to antibiotic treatments. However, dormant bacteria regain growth and virulence when the immune system is weakened, leading again to the active form of the disease...
June 3, 2017: Biochimie
https://www.readbyqxmd.com/read/28584959/preventing-tuberculosis-in-a-low-incidence-setting-evaluation-of-a-multi-lingual-online-educational-video-on-latent-tuberculosis
#17
Jie Gao, Victoria J Cook, Maureen Mayhew
Treating latent tuberculosis infection (LTBI) in those at risk is an important yet challenging cornerstone of TB elimination. We evaluated a culturally-tailored, multi-lingual, 4.5-min, health promotional video on LTBI. Mixed methods study assessed use of the video with web-analytics, acceptability of content through interviews and survey questions, and compared knowledge scores in viewers and non-viewers using a survey. The video was viewed 6999 times in six languages over 1 year. Of 1598 survey respondents, 193 viewers had a mean knowledge score of 59%, compared to 38% in non-viewers...
June 5, 2017: Journal of Immigrant and Minority Health
https://www.readbyqxmd.com/read/28579606/isoniazid-prophylaxis-for-latent-tuberculosis-infections-in-liver-transplant-recipients-in-a-tuberculosis-endemic-area
#18
Hyung Hwan Moon, So Yeon Park, Jong Man Kim, Jae Berm Park, Choon Hyuck David Kwon, Kyong Ran Peck, Sung-Joo Kim, Suk-Koo Lee, Jae-Won Joh
BACKGROUND Isoniazid (INH) prophylaxis (Px) has good efficacy for preventing tuberculosis (TB) in the general population. However, its use for the treatment of latent TB infections (LTBI) in liver transplant (LT) recipients is challenging because little is known about INH-induced hepatotoxicity in graft recipients. We evaluated the efficacy and safety of INH Px in LT recipients. MATERIAL AND METHODS From March 2008 to December 2012, we retrospectively reviewed data on 277 patients who received LT at a single center...
June 5, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28578689/race-and-nativity-are-major-determinants-of-tuberculosis-in-the-u-s-evidence-of-health-disparities-in-tuberculosis-incidence-in-michigan-2004-2012
#19
Grace A Noppert, Mark L Wilson, Philippa Clarke, Wen Ye, Peter Davidson, Zhenhua Yang
BACKGROUND: The incidence of TB in Michigan was 1.5 per 100,000 people in 2012, roughly half the U.S. incidence. Despite successes in TB control, disparities in TB still exist in Michigan, particularly by race, age, and nativity. A major challenge in understanding disparities in TB burden is distinguishing between TB cases resulting from recent transmission and those resulting from reactivation of latent TB infection, information critical to tailoring control strategies. We examined nine-year trends in tuberculosis (TB) incidence patterns for the entire population of Michigan, and within demographic subgroups...
June 2, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28575319/translational-research-in-the-nonhuman-primate-model-of-tuberculosis
#20
Taylor W Foreman, Smriti Mehra, Andrew A Lackner, Deepak Kaushal
Infection with Mycobacterium tuberculosis predominantly establishes subclinical latent infection over the lifetime of an individual, with a fraction of infected individuals rapidly progressing to active disease. The immune control in latent infection can be perturbed by comorbidities such as diabetes mellitus, obesity, smoking, and coinfection with helminthes or HIV. Modeling the varying aspects of natural infection remains incomplete when using zebrafish and mice. However, the nonhuman primate model of tuberculosis offers a unique and accurate model to investigate host responses to infection, test novel therapeutics, and thoroughly assess preclinical vaccine candidates...
May 31, 2017: ILAR Journal
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