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https://www.readbyqxmd.com/read/28934844/an-update-on-cardiomyopathies-immune-mediated-diseases-sarcoidosis-and-peripartum-and-hypertrophic-cardiomyopathies-during-pregnancy
#1
Thomas F Lüscher
No abstract text is available yet for this article.
September 14, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28934695/type-1-diabetes-and-viral-infections-what-is-the-relationship
#2
REVIEW
Nicola Principi, Maria Giulia Berioli, Sonia Bianchini, Susanna Esposito
Type 1 diabetes (T1D) is the most common chronic metabolic disorder in children. Epigenetic and environmental factors capable of altering the penetrance of major susceptibility genes or capable of increasing the penetrance of low-risk genes are currently thought to play a role in triggering autoimmunity and T1D development. This paper discusses the current knowledge of the role of viruses in T1D. Most studies that have evaluated the potential association between viral infections and T1D have indicated that it is highly likely that some of these infectious agents play a role in T1D development...
September 8, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28934595/copd-alters-immune-cell-composition-and-immune-checkpoint-inhibitor-efficacy-in-nsclc
#3
Nicholas M Mark, Julia Kargl, Stephanie E Busch, Grace H Y Yang, Heather E Metz, Huajia Zhang, Jesse J Hubbard, Sudhakar N J Pipavath, David K Madtes, A McGarry Houghton
RATIONALE: Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are interrelated diseases with substantial mortality; the pathogenesis of both involves aberrant immune functioning. OBJECTIVE: To profile the immune cell composition and function in patients with NSCLC and describe the effect of COPD on lung and tumor microenvironments. METHODS: We profiled resected lung and tumor tissue using flow cytometry and T-cell receptor sequencing in patients with and without COPD from a prospective cohort of patients undergoing resection of NSCLC...
September 21, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28934563/hemophagocytic-lymphohistiocytosis
#4
Hanny Al-Samkari, Nancy Berliner
Hemophagocytic lymphohistiocytosis is a life-threatening disorder characterized by unbridled activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages resulting in hypercytokinemia and immunemediated injury of multiple organ systems. It is seen in both children and adults and is recognized as primary (driven by underlying genetic mutations that abolish critical proteins required for normal function of cytotoxic T cells and NK cells) or secondary (resulting from a malignant, infectious, or autoimmune stimulus without an identifiable underlying genetic trigger)...
September 13, 2017: Annual Review of Pathology
https://www.readbyqxmd.com/read/28934479/targeted-reconstruction-of-t-cell-receptor-sequence-from-single-cell-rna-seq-links-cdr3-length-to-t-cell-differentiation-state
#5
Shaked Afik, Kathleen B Yates, Kevin Bi, Samuel Darko, Jernej Godec, Ulrike Gerdemann, Leo Swadling, Daniel C Douek, Paul Klenerman, Eleanor J Barnes, Arlene H Sharpe, W Nicholas Haining, Nir Yosef
The T cell compartment must contain diversity in both T cell receptor (TCR) repertoire and cell state to provide effective immunity against pathogens. However, it remains unclear how differences in the TCR contribute to heterogeneity in T cell state. Single cell RNA-sequencing (scRNA-seq) can allow simultaneous measurement of TCR sequence and global transcriptional profile from single cells. However, current methods for TCR inference from scRNA-seq are limited in their sensitivity and require long sequencing reads, thus increasing the cost and decreasing the number of cells that can be feasibly analyzed...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934453/an-adjuvanted-a-h5n1-subvirion-vaccine-elicits-virus-specific-antibody-response-and-improves-protection-against-lethal-influenza-viral-challenge-in-mouse-model-of-protein-energy-malnutrition
#6
Enitra N Jones, Samuel Amoah, Weiping Cao, Suryaprakash Sambhara, Shivaprakash Gangappa
Background: Protein energy malnutrition (PEM) increases susceptibility to infectious diseases, including influenza infection, but no studies have addressed the potential influences of PEM on the immunogenicity and protective efficacy of avian influenza A(H5N1) vaccine. Methods: We investigated the role of PEM on vaccine-mediated protection after a lethal challenge with recombinant A(H5N1) virus using isocaloric diets providing either adequate protein (AP; 18% protein) or very low protein (VLP; 2% protein) in an established murine model of influenza vaccination...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934435/declining-transmission-and-immunity-to-malaria-and-emerging-artemisinin-resistance-in-thailand-a-longitudinal-study
#7
Ricardo Ataíde, Rosanna Powell, Kerryn Moore, Alistair McLean, Aung Pyae Phyo, Shalini Nair, Marina White, Tim J Anderson, James G Beeson, Julie A Simpson, Francois Nosten, Freya J I Fowkes
Background: Reductions in malaria transmission decrease naturally acquired immunity, which may influence the emergence of Plasmodium falciparum artemisinin-resistant phenotypes and genotypes over time. Methods: Antibodies specific for P. falciparum antigens were determined in uncomplicated hyperparasitemic malaria patients over a 10-year period of declining malaria transmission and emerging artemisinin resistance in northwestern Thailand. We investigated the association between antibody levels and both parasite clearance time (PCt½) and artemisinin resistance-associated kelch13 genotypes over time...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934428/hiv-infected-children-have-elevated-levels-of-pd-1-memory-cd4-t-cells-with-low-proliferative-capacity-and-high-inflammatory-cytokine-effector-functions
#8
Julia Foldi, Lina Kozhaya, Bret McCarty, Mussa Mwamzuka, Fatma Marshed, Tiina Ilmet, Max Kilberg, Adam Kravietz, Aabid Ahmed, William Borkowsky, Derya Unutmaz, Alka Khaitan
Background: During human immunodeficiency virus (HIV) disease, chronic immune activation leads to T-cell exhaustion. PD-1 identifies "exhausted" CD8 T cells with impaired HIV-specific effector functions, but its role on CD4 T cells and in HIV-infected children is poorly understood. Methods: In a Kenyan cohort of vertically HIV-infected children, we measured PD-1+ CD4 T-cell frequencies and phenotype by flow cytometry and their correlation with HIV disease progression and immune activation...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934427/immunologic-profiling-of-human-metapneumovirus-for-the-development-of-targeted-immunotherapy
#9
Ifigeneia Tzannou, Sarah K Nicholas, Premal Lulla, Paibel I Aguayo-Hiraldo, Anisha Misra, Caridad A Martinez, Annette A Machado, Jordan S Orange, Pedro A Piedra, Juan F Vera, Ann M Leen
Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934426/enhanced-macrophage-m1-polarization-and-resistance-to-apoptosis-enable-resistance-to-plague
#10
Emilia Pachulec, Rym Ben Abdelwahed Bagga, Lucie Chevallier, Hope O'Donnell, Chloé Guillas, Jean Jaubert, Xavier Montagutelli, Elisabeth Carniel, Christian E Demeure
Background: Susceptibility to infection is in part genetically driven, and C57BL/6 mice resist various pathogens through the proinflammatory response of their M1 macrophages (MPs). However, they are susceptible to plague. It has been reported elsewhere that Mus spretus SEG mice resist plague and develop an immune response characterized by a strong recruitment of MPs. Methods: The responses of C57BL/6 and SEG MPs exposed to Yersinia pestis in vitro were examined...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934424/the-impact-of-hepatitis-b-vaccine-failure-on-long-term-natural-course-of-chronic-hepatitis-b-virus-infection-in-hepatitis-b-e-antigen-seropositive-children
#11
Chi-San Tai, Jia-Feng Wu, Huey-Ling Chen, Yen-Hsuan Ni, Hong-Yuan Hsu, Mei-Hwei Chang
Background: Vaccine failure with chronic hepatitis B virus (HBV) infection still develops in children after universal hepatitis B immunization. This study aimed to investigate the natural course of chronic HBV infection in children with vaccine failure and compare it with that of nonvaccinated children. Methods: Three hundred fifty-six hepatitis B e antigen (HBeAg)-seropositive, hepatitis B surface antigen (HBsAg) carrier children, who were followed for at least 1 year without antiviral therapy, were enrolled...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934421/a-zebrafish-model-of-mycobacterium-leprae-granulomatous-infection
#12
Cressida A Madigan, James Cameron, Lalita Ramakrishnan
Understanding the pathogenesis of leprosy granulomas has been hindered by a paucity of tractable experimental animal models. Mycobacterium leprae, which causes leprosy, grows optimally at approximately 30°C, so we sought to model granulomatous disease in the ectothermic zebrafish. We found that noncaseating granulomas develop rapidly and eventually eradicate infection. rag1 mutant zebrafish, which lack lymphocytes, also form noncaseating granulomas with similar kinetics, but these control infection more slowly...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934369/in-vivo-activation-of-latent-hiv-with-a-synthetic-bryostatin-analog-effects-both-latent-cell-kick-and-kill-in-strategy-for-virus-eradication
#13
Matthew D Marsden, Brian A Loy, Xiaomeng Wu, Christina M Ramirez, Adam J Schrier, Danielle Murray, Akira Shimizu, Steven M Ryckbosch, Katherine E Near, Tae-Wook Chun, Paul A Wender, Jerome A Zack
The ability of HIV to establish a long-lived latent infection within resting CD4+ T cells leads to persistence and episodic resupply of the virus in patients treated with antiretroviral therapy (ART), thereby preventing eradication of the disease. Protein kinase C (PKC) modulators such as bryostatin 1 can activate these latently infected cells, potentially leading to their elimination by virus-mediated cytopathic effects, the host's immune response and/or therapeutic strategies targeting cells actively expressing virus...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28934360/pkacs-attenuate-innate-antiviral-response-by-phosphorylating-visa-and-priming-it-for-march5-mediated-degradation
#14
Bing-Ru Yan, Lu Zhou, Ming-Ming Hu, Mi Li, Heng Lin, Yan Yang, Yan-Yi Wang, Hong-Bing Shu
Sensing of viral RNA by RIG-I-like receptors initiates innate antiviral response, which is mediated by the central adaptor VISA. How the RIG-I-VISA-mediated antiviral response is terminated at the late phase of infection is enigmatic. Here we identified the protein kinase A catalytic (PKAC) subunits α and β as negative regulators of RNA virus-triggered signaling in a redundant manner. Viral infection up-regulated cellular cAMP levels and activated PKACs, which then phosphorylated VISA at T54. This phosphorylation abrogated virus-induced aggregation of VISA and primed it for K48-linked polyubiquitination and degradation by the E3 ligase MARCH5, leading to attenuation of virus-triggered induction of downstream antiviral genes...
September 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28934357/from-bacterial-killing-to-immune-modulation-recent-insights-into-the-functions-of-lysozyme
#15
REVIEW
Stephanie A Ragland, Alison K Criss
Lysozyme is a cornerstone of innate immunity. The canonical mechanism for bacterial killing by lysozyme occurs through the hydrolysis of cell wall peptidoglycan (PG). Conventional type (c-type) lysozymes are also highly cationic and can kill certain bacteria independently of PG hydrolytic activity. Reflecting the ongoing arms race between host and invading microorganisms, both gram-positive and gram-negative bacteria have evolved mechanisms to thwart killing by lysozyme. In addition to its direct antimicrobial role, more recent evidence has shown that lysozyme modulates the host immune response to infection...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28934318/identification-of-lag3-high-affinity-aptamers-by-ht-selex-and-conserved-motif-accumulation-cma
#16
Mario Martínez Soldevilla, Sandra Hervas, Helena Villanueva, Teresa Lozano, Obdulia Rabal, Julen Oyarzabal, Juan José Lasarte, Maurizio Bendandi, Susana Inoges, Ascensión López-Díaz de Cerio, Fernando Pastor
LAG3 receptor belongs to a family of immune-checkpoints expressed in T lymphocytes and other cells of the immune system. It plays an important role as a rheostat of the immune response. Focus on this receptor as a potential therapeutic target in cancer immunotherapy has been underscored after the success of other immune-checkpoint blockade strategies in clinical trials. LAG3 showcases the interest in the field of autoimmunity as several studies show that LAG3-targeting antibodies can also be used for the treatment of autoimmune diseases...
2017: PloS One
https://www.readbyqxmd.com/read/28934252/three-way-interaction-model-to-trace-the-mechanisms-involved-in-alzheimer-s-disease-transgenic-mice
#17
Nasibeh Khayer, Sayed-Amir Marashi, Mehdi Mirzaie, Fatemeh Goshadrou
Alzheimer's disease (AD) is the most common cause for dementia in human. Currently, more than 46 million people in the world suffer from AD and it is estimated that by 2050 this number increases to more than 131 million. AD is considered as a complex disease. Therefore, understanding the mechanism of AD is a universal challenge. Nowadays, a huge number of disease-related high-throughput "omics" datasets are freely available. Such datasets contain valuable information about disease-related pathways and their corresponding gene interactions...
2017: PloS One
https://www.readbyqxmd.com/read/28934246/discovery-of-pf-06928215-as-a-high-affinity-inhibitor-of-cgas-enabled-by-a-novel-fluorescence-polarization-assay
#18
Justin Hall, Amy Brault, Fabien Vincent, Shawn Weng, Hong Wang, Darren Dumlao, Ann Aulabaugh, Dikran Aivazian, Dana Castro, Ming Chen, Jeffrey Culp, Ken Dower, Joseph Gardner, Steven Hawrylik, Douglas Golenbock, David Hepworth, Mark Horn, Lyn Jones, Peter Jones, Eicke Latz, Jing Li, Lih-Ling Lin, Wen Lin, David Lin, Frank Lovering, Nootaree Niljanskul, Ryan Nistler, Betsy Pierce, Olga Plotnikova, Daniel Schmitt, Suman Shanker, James Smith, William Snyder, Timothy Subashi, John Trujillo, Edyta Tyminski, Guoxing Wang, Jimson Wong, Bruce Lefker, Leslie Dakin, Karen Leach
Cyclic GMP-AMP synthase (cGAS) initiates the innate immune system in response to cytosolic dsDNA. After binding and activation from dsDNA, cGAS uses ATP and GTP to synthesize 2', 3' -cGAMP (cGAMP), a cyclic dinucleotide second messenger with mixed 2'-5' and 3'-5' phosphodiester bonds. Inappropriate stimulation of cGAS has been implicated in autoimmune disease such as systemic lupus erythematosus, thus inhibition of cGAS may be of therapeutic benefit in some diseases; however, the size and polarity of the cGAS active site makes it a challenging target for the development of conventional substrate-competitive inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28934245/angiopoietin-like-protein-2-regulates-porphyromonas-gingivalis-lipopolysaccharide-induced-inflammatory-response-in-human-gingival-epithelial-cells
#19
Tasuku Ohno, Genta Yamamoto, Jun-Ichiro Hayashi, Eisaku Nishida, Hisashi Goto, Yasuyuki Sasaki, Takeshi Kikuchi, Mitsuo Fukuda, Yoshiaki Hasegawa, Makio Mogi, Akio Mitani
Angiopoietin-like protein 2 (ANGPTL2) maintains tissue homeostasis by inducing inflammation and angiogenesis. It is produced in infiltrating immune cells or resident cells, such as adipocytes, vascular endothelial cells, and tumor cells. We hypothesized that ANGPTL2 might play an important role as a unique mediator in both systemic and periodontal disease. We demonstrated an increased ANGPTL2 concentration in gingival crevicular fluid from chronic periodontitis patients. Porphyromonas gingivalis lipopolysaccharide (LPS) treatment strongly induced ANGPTL2 mRNA and protein levels in Ca9-22 human gingival epithelial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28934241/hla-dr7-and-hla-dq2-transgenic-mouse-strains-tested-as-a-model-system-for-ximelagatran-hepatotoxicity
#20
Hanna Lundgren, Klara Martinsson, Karin Cederbrant, Johan Jirholt, Daniel Mucs, Katja Madeyski-Bengtson, Said Havarinasab, Per Hultman
The oral thrombin inhibitor ximelagatran was withdrawn in the late clinical trial phase because it adversely affected the liver. In approximately 8% of treated patients, drug-induced liver injury (DILI) was expressed as transient alanine transaminase (ALT) elevations. No evidence of DILI had been revealed in the pre-clinical in vivo studies. A whole genome scan study performed on the clinical study material identified a strong genetic association between the major histocompatibility complex alleles for human leucocyte antigens (HLA) (HLA-DR7 and HLA-DQ2) and elevated ALT levels in treated patients...
2017: PloS One
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