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https://www.readbyqxmd.com/read/27906487/neutrophil-activation-during-acute-human-anaphylaxis-analysis-of-mpo-and-scd62l
#1
Abbie Francis, Erika Bosio, Shelley F Stone, Daniel M Fatovich, Glenn Arendts, Yusuf Nagree, Stephen P J Macdonald, Hugh Mitenko, Mani Rajee, Sally Burrows, Simon G A Brown
BACKGROUND: The mechanisms involved in the amplification of the mast cell response during anaphylaxis are unclear. Mouse models of anaphylaxis demonstrate the critical involvement of neutrophils. These innate immune cells are highly abundant in peripheral blood and can be rapidly activated to trigger both local and systemic inflammation. OBJECTIVE: To investigate neutrophil activation in peripheral blood during acute human anaphylaxis. METHODS: Patients presenting to the Emergency Department with anaphylaxis underwent blood sampling upon enrolment and at up to three subsequent time points...
December 1, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27906454/immunotherapy-of-head-and-neck-cancer-emerging-clinical-trials-from-a-national-cancer-institute-head-and-neck-cancer-steering-committee-planning-meeting
#2
Julie E Bauman, Ezra Cohen, Robert L Ferris, David J Adelstein, David M Brizel, John A Ridge, Brian O'Sullivan, Barbara A Burtness, Lisa H Butterfield, William E Carson, Mary L Disis, Bernard A Fox, Thomas F Gajewski, Maura L Gillison, James W Hodge, Quynh-Thu Le, David Raben, Scott E Strome, Jean Lynn, Shakun Malik
Recent advances have permitted successful therapeutic targeting of the immune system in head and neck squamous cell carcinoma (HNSCC). These new immunotherapeutic targets and agents are being rapidly adopted by the oncologic community and hold considerable promise. The National Cancer Institute sponsored a Clinical Trials Planning Meeting to address the issue of how to further investigate the use of immunotherapy in patients with HNSCC. The goals of the meeting were to consider phase 2 or 3 trial designs primarily in 3 different patient populations: those with previously untreated, human papillomavirus-initiated oropharyngeal cancers; those with previously untreated, human papillomavirus-negative HNSCC; and those with recurrent/metastatic HNSCC...
December 1, 2016: Cancer
https://www.readbyqxmd.com/read/27906453/syk-inhibition-blocks-airway-constriction-and-protects-from-th2-induced-airway-inflammation-and-remodeling-in-mice
#3
Christoph Tabeling, Julia Herbert, Andreas C Hocke, David Lamb, Lutz Wollin, Klaus Erb, Ekaterina Boiarina, Hesam Movassagh, Jörg Scheffel, Jan M Doehn, Stefan Hippenstiel, Marcus Maurer, Abdelilah S Gounni, Wolfgang M Kuebler, Norbert Suttorp, Martin Witzenrath
BACKGROUND: Spleen tyrosine kinase (Syk) is an intracellular non-receptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive. METHODS: Spectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression...
December 1, 2016: Allergy
https://www.readbyqxmd.com/read/27906187/systemic-application-of-3-methyladenine-markedly-inhibited-atherosclerotic-lesion-in-apoe-mice-by-modulating-autophagy-foam-cell-formation-and-immune-negative-molecules
#4
Shen Dai, Bo Wang, Wen Li, Liyang Wang, Xingguo Song, Chun Guo, Yulan Li, Fengming Liu, Faliang Zhu, Qun Wang, Xiaoyan Wang, Yongyu Shi, Jianing Wang, Wei Zhao, Lining Zhang
A growing body of evidence demonstrates that autophagy, an evolutionarily conserved intracellular degradation process, is involved in the pathogenesis of atherosclerosis and has become a potential therapeutic target. Here we tested the effect of two inhibitors of phosphatidylinositol 3-kinase, 3-methyladenine (3-MA) and 2-(4-morpholinyl)-8-phenyl-chromone (LY294002), commonly used as inhibitors of autophagy, in atherosclerosis in apolipoprotein E(-/-) mice. Systemic application of 3-MA but not LY294002 markedly reduced the size of atherosclerotic plaque and increased the stability of lesions in high-fat diet-fed mice as compared with controls...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906186/preimplantation-factor-is-an-anti-apoptotic-effector-in-human-trophoblasts-involving-p53-signaling-pathway
#5
Hadia Moindjie, Esther Dos Santos, Rita-Josiane Gouesse, Nelly Swierkowski-Blanchard, Valérie Serazin, Eytan R Barnea, François Vialard, Marie-Noëlle Dieudonné
From the earliest stages of gestation, embryonic-maternal interaction has a key role in a successful pregnancy. Various factors present during gestation may significantly influence this type of juxta/paracrine interaction. PreImplantation Factor (PIF) is a recently identified factor with activity at the fetomaternal interface. PIF is secreted by viable embryos and directly controls placental development by increasing the invasive capacity of human extravillous trophoblasts (EVTs). To further specify PIF's role in the human placenta, we analyzed the genome-wide expression profile of the EVT in the presence of a synthetic PIF analog (sPIF)...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906184/1-methyl-tryptophan-attenuates-regulatory-t-cells-differentiation-due-to-the-inhibition-of-estrogen-ido1-mrc2-axis-in-endometriosis
#6
Chunyan Wei, Jie Mei, Lingli Tang, Yukai Liu, Dajin Li, Mingqing Li, Xiaoyong Zhu
Foxp3(+) regulatory T (Treg) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal Treg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal Treg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906162/activation-of-myeloid-and-endothelial-cells-by-cd40l-gene-therapy-supports-t-cell-expansion-and-migration-into-the-tumor-microenvironment
#7
E Eriksson, R Moreno, I Milenova, L Liljenfeldt, L C Dieterich, L Christiansson, H Karlsson, G Ullenhag, S Mangsbo, A Dimberg, R Alemany, A Loskog
CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate Th1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer...
December 1, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27906073/gut-barrier-structure-mucosal-immunity-and-intestinal-microbiota-in-the-pathogenesis-and-treatment-of-hiv-infection
#8
REVIEW
Camilla Tincati, Daniel C Douek, Giulia Marchetti
Over the past 10 years, extensive work has been carried out in the field of microbial translocation in HIV infection, ranging from studies on its clinical significance to investigations on its pathogenic features. In the present work, we review the most recent findings on this phenomenon, focusing on the predictive role of microbial translocation in HIV-related morbidity and mortality, the mechanisms by which it arises and potential therapeutic approaches. From a clinical perspective, current work has shown that markers of microbial translocation may be useful in predicting clinical events in untreated HIV infection, while conflicting data exist on their role in cART-experienced subjects, possibly due to the inclusion of extremely varied patient populations in cohort studies...
April 11, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27906052/antibody-responses-to-de-novo-identified-citrullinated-fibrinogen-peptides-in-rheumatoid-arthritis-and-visualization-of-the-corresponding-b-cells
#9
Vijay Joshua, Loes Schobers, Philip J Titcombe, Lena Israelsson, Johan Rönnelid, Monika Hansson, Anca I Catrina, Ger J M Pruijn, Vivianne Malmström
BACKGROUND: Antibodies against citrullinated proteins (ACPA) are common in patients with rheumatoid arthritis (RA). ACPA can appear before disease onset and target many self-antigens. Citrullinated fibrin/fibrinogen represents a classical ACPA target antigen, and mass spectrometry of RA synovial fluid reveals elevated citrullinated (cit) fibrinogen (Fib) peptides compared to non-RA controls. We investigated the extent to which these less-studied peptides represent autoantibody targets and sought to visualize the corresponding cit-Fib-reactive B cells in RA patients...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27906022/risk-factors-for-unstructured-treatment-interruptions-and-association-with-survival-in-low-to-middle-income-countries
#10
James H McMahon, Tim Spelman, Nathan Ford, Jane Greig, Anita Mesic, Charles Ssonko, Esther C Casas, Daniel P O'Brien
BACKGROUND: Antiretroviral therapy (ART) treatment interruptions lead to poor clinical outcomes with unplanned or unstructured TIs (uTIs) likely to be underreported. This study describes; uTIs, their risk factors and association with survival. METHODS: Analysis of ART programmatic data from 11 countries across Asia and Africa between 2003 and 2013 where an uTI was defined as a ≥90-day patient initiated break from ART calculated from the last day the previous ART prescription would have run out until the date of the next ART prescription...
July 11, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27906009/current-trends-and-intricacies-in-the-management-of-hiv-associated-pulmonary-tuberculosis
#11
REVIEW
Narendran Gopalan, Padmapriyadarsini Chandrasekaran, Soumya Swaminathan, Srikanth Tripathy
Human immunodeficiency virus (HIV) epidemic has undoubtedly increased the incidence of tuberculosis (TB) globally, posing a formidable global health challenge affecting 1.2 million cases. Pulmonary TB assumes utmost significance in the programmatic perspective as it is readily transmissible as well as easily diagnosable. HIV complicates every aspect of pulmonary tuberculosis from diagnosis to treatment, demanding a different approach to effectively tackle both the diseases. In order to control these converging epidemics, it is important to diagnose early, initiate appropriate therapy for both infections, prevent transmission and administer preventive therapy...
September 26, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27906006/integrated-therapy-for-hiv-and-tuberculosis
#12
REVIEW
Weerawat Manosuthi, Surasak Wiboonchutikul, Somnuek Sungkanuparph
Tuberculosis (TB) has been the most common opportunistic infection and cause of mortality among HIV-infected patients, especially in resource-limited countries. Clinical manifestations of TB vary and depend on the degree of immunodeficiency. Sputum microscopy and culture with drug-susceptibility testing are recommended as a standard method for diagnosing active TB. TB-related mortality in HIV-infected patients is high especially during the first few months of treatment. Integrated therapy of both HIV and TB is feasible and efficient to control the diseases and yield better survival...
May 12, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27906005/the-role-of-nk-cells-in-hiv-1-protection-autologous-allogeneic-or-both
#13
REVIEW
Jef Hens, Wim Jennes, Luc Kestens
Natural killer (NK) cells specialize in killing virally infected- or tumor cells and are part of the innate immune system. The activational state of NK cells is determined by the balance of incoming activating and inhibitory signals mediated by receptor-ligand binding with the target cell. These receptor-ligand bonds mainly consist of the killer immunoglobulin-like receptors (KIR), which are expressed at the cell surface of NK cells, and their ligands: the highly variable human leukocyte antigen -class I molecules (HLA)...
March 18, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27905838/engineering-hiv-specific-immunity-with-chimeric-antigen-receptors
#14
Scott G Kitchen, Jerome A Zack
HIV remains a highly important public health and clinical issue despite many recent advances in attempting to develop a cure, which has remained elusive for most people infected with HIV. HIV disease can be controlled with pharmacologic therapies; however, these treatments are expensive, may have severe side effects, and are not curative. Consequently, an improved means to control or eliminate HIV replication is needed. Cytotoxic T lymphocytes (CTLs) play a critical role in controlling viral replication and are an important part in the ability of the immune response to eradicate most viral infections...
December 2016: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/27905837/long-term-persistence-of-immunity-after-hepatitis-b-vaccination-a-fact-not-a-fancy
#15
Andrea Trevisan
On the basis of an article previously published in the journal regarding immune persistence after hepatitis B vaccination in infancy, I discuss why this persistence is a fact and not a fancy. Immune memory after a primary vaccination series has been widely demonstrated by prompt response to booster doses and the proliferation of T cells secreting IFNγ. In a large cohort of medical students, 79% of subjects were positive for anti-HBs antibodies, and only 1.9% of the subjects had serological evidence of past hepatitis B infection...
December 1, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27905556/cellular-aspartyl-proteases-promote-the-unconventional-secretion-of-biologically-active-hiv-1-matrix-protein-p17
#16
Francesca Caccuri, Maria Luisa Iaria, Federica Campilongo, Kristen Varney, Alessandro Rossi, Stefania Mitola, Silvia Schiarea, Antonella Bugatti, Pietro Mazzuca, Cinzia Giagulli, Simona Fiorentini, Wuyuan Lu, Mario Salmona, Arnaldo Caruso
The human immune deficiency virus type 1 (HIV-1) matrix protein p17 (p17), although devoid of a signal sequence, is released by infected cells and detected in blood and in different organs and tissues even in HIV-1-infected patients undergoing successful combined antiretroviral therapy (cART). Extracellularly, p17 deregulates the function of different cells involved in AIDS pathogenesis. The mechanism of p17 secretion, particularly during HIV-1 latency, still remains to be elucidated. A recent study showed that HIV-1-infected cells can produce Gag without spreading infection in a model of viral latency...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905535/bordetella-pertussis-outer-membrane-vesicle-vaccine-confers-equal-efficacy-in-mice-with-milder-inflammatory-responses-compared-to-a-whole-cell-vaccine
#17
René H M Raeven, Jolanda Brummelman, Jeroen L A Pennings, Larissa van der Maas, Wichard Tilstra, Kina Helm, Elly van Riet, Wim Jiskoot, Cécile A C M van Els, Wanda G H Han, Gideon F A Kersten, Bernard Metz
The demand for improved pertussis vaccines is urgent due to the resurgence of whooping cough. A deeper understanding of the mode of action of pertussis vaccines is required to achieve this improvement. The vaccine-induced effects of a candidate outer membrane vesicle vaccine (omvPV) and a classical protective but reactogenic whole cell vaccine (wPV) were comprehensively compared in mice. The comparison revealed essential qualitative and quantitative differences with respect to immunogenicity and adverse effects for these vaccines...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905502/immune-responsiveness-of-cd4-t-cells-during-streptococcus-suis-serotype-2-infection
#18
Marie-Pier Lecours, Corinne Letendre, Damian Clarke, Paul Lemire, Tristan Galbas, Marie-Odile Benoit-Biancamano, Jacques Thibodeau, Marcelo Gottschalk, Mariela Segura
The pathogenesis of Streptococcus suis infection, a major swine and human pathogen, is only partially understood and knowledge on the host adaptive immune response is critically scarce. Yet, S. suis virulence factors, particularly its capsular polysaccharide (CPS), enable this bacterium to modulate dendritic cell (DC) functions and potentially impair the immune response. This study aimed to evaluate modulation of T cell activation during S. suis infection and the role of DCs in this response. S. suis-stimulated total mouse splenocytes readily produced TNF-α, IL-6, IFN-γ, CCL3, CXCL9, and IL-10...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905482/pharmacologic-modulation-of-ror%C3%AE-t-translates-to-efficacy-in-preclinical-and-translational-models-of-psoriasis-and-inflammatory-arthritis
#19
Xiaohua Xue, Pejman Soroosh, Aimee De Leon-Tabaldo, Rosa Luna-Roman, Marciano Sablad, Natasha Rozenkrants, Jingxue Yu, Glenda Castro, Homayon Banie, Wai-Ping Fung-Leung, Luis Santamaria-Babi, Thomas Schlueter, Michael Albers, Kristi Leonard, Alison L Budelsky, Anne M Fourie
The IL-23/IL-17 pathway is implicated in autoimmune diseases, particularly psoriasis, where biologics targeting IL-23 and IL-17 have shown significant clinical efficacy. Retinoid-related orphan nuclear receptor gamma t (RORγt) is required for Th17 differentiation and IL-17 production in adaptive and innate immune cells. We identified JNJ-54271074, a potent and highly-selective RORγt inverse agonist, which dose-dependently inhibited RORγt-driven transcription, decreased co-activator binding and promoted interaction with co-repressor protein...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905296/a-pathogenic-role-for-the-integrin-cd103-in-experimental-allergic-airways-disease
#20
Vanessa S Fear, Siew Ping Lai, Graeme R Zosky, Kara L Perks, Shelley Gorman, Fabian Blank, Christophe von Garnier, Philip A Stumbles, Deborah H Strickland
The integrin CD103 is the αE chain of integrin αEβ7 that is important in the maintenance of intraepithelial lymphocytes and recruitment of T cells and dendritic cells (DC) to mucosal surfaces. The role of CD103 in intestinal immune homeostasis has been well described, however, its role in allergic airway inflammation is less well understood. In this study, we used an ovalbumin (OVA)-induced, CD103-knockout (KO) BALB/c mouse model of experimental allergic airways disease (EAAD) to investigate the role of CD103 in disease expression, CD4(+) T-cell activation and DC activation and function in airways and lymph nodes...
November 2016: Physiological Reports
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