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https://www.readbyqxmd.com/read/28931895/defective-thymic-output-in-was-patients-is-associated-with-abnormal-actin-organization
#1
Wenyan Li, Xiaoyu Sun, Jinzhi Wang, Qin Zhao, Rongxin Dai, Yanping Wang, Lina Zhou, Lisa Westerberg, Yuan Ding, Xiaodong Zhao, Chaohong Liu
Wiskott-Aldrich syndrome protein (WASp) is a key regulator of the actin cytoskeleton. Defective T - cell function is a major cause for immune deficiency in Wiskott-Aldrich syndrome (WAS) patients. T cells originate in the bone marrow and develop in the thymus, and then migrate to peripheral tissues. TCR excision circles (TRECs) present in thymic output cells stably, which is used as a molecular marker for thymic output. We found that CD8(+) T naïve cells of classic WAS patients were significantly reduced, and TRECs in patients with classic WAS and X-linked thrombocytopenia (XLT) dramatically decreased compared with that of HCs...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28926774/concurrent-administration-effect-of-antibiotic-and-anti-inflammatory-drugs-on-the-immunotoxicity-of-bacterial-endotoxins
#2
Azza M El Amir, Dalia G Tanious, Hanaa A Mansour
Pseudomonas aeruginosa (P. aeruginosa) is a gram-negative bacterium that causes a variety of diseases in compromised hosts. Bacterial endotoxins such as lipopolysaccharide (LPS) are the major outer surface membrane components that are present in almost all gram-negative bacteria and act as extremely strong stimulators of innate immunity and inflammation of the airway. This study was undertaken to determine the effect of combined administration of Gentamicin (GENT) as an antibiotic and Dexamethasone (DEXA) as an anti-inflammatory drug on some immunological and histological parameters...
September 16, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28916969/comparison-of-platelet-lymphocyte-ratio-and-ca-19-9-in-differentiating-benign-from-malignant-head-masses-in-patients-with-chronic-pancreatitis
#3
Shanavas Kakkat, Ramesh Rajan, R S Sindhu, Bonny Natesh, S Raviram
INTRODUCTION: Pancreatic head ductal adenocarcinoma (PDAC) and inflammatory head masses (IHM) related to chronic pancreatitis are often difficult to differentiate. PDAC produces significant inflammatory response with resultant lymphopenia and thrombocytosis. The prognostic role of platelet-lymphocyte ratio (PLR) as a tumor marker has been defined. We aimed to find the role of PLR as a diagnostic marker for PDAC in differentiating benign head mass comparing with carbohydrate antigen 19-9 (CA 19-9)...
September 16, 2017: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
https://www.readbyqxmd.com/read/28915584/a-phase-1-dose-escalation-study-of-the-oral-histone-deacetylase-inhibitor-abexinostat-in-combination-with-standard-hypofractionated-radiotherapy-in-advanced-solid-tumors
#4
Eric Deutsch, Elizabeth Cohen-Jonathan Moyal, Vanesa Gregorc, Paolo Andrea Zucali, Jean Menard, Jean-Charles Soria, Ioana Kloos, Jeff Hsu, Ying Luan, Emily Liu, Remus Vezan, Thorsten Graef, Sofia Rivera
Current treatments for advanced solid tumors tend to be only palliative. Although radiotherapy is administered with a curative intent, radioresistance and dose-limiting toxicities pose limitations to treatment. Abexinostat, an oral pan-histone deacetylase inhibitor, demonstrated enhanced sensitivity to radiation in various solid tumor cell lines. We conducted an exploratory, phase 1, dose-escalation study of abexinostat in combination with standard hypofractionated radiotherapy in patients with advanced solid tumors treated in a palliative setting...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914581/circulating-lymphocyte-levels-and-relationship-with-infection-status-in-patients-with-relapsing-remitting-multiple-sclerosis-treated-with-daclizumab-beta
#5
Gavin Giovannoni, Heinz Wiendl, Benjamin Turner, Kimberly Umans, Oksana Mokliatchouk, Wanda Castro-Borrero, Steven J Greenberg, Peter McCroskery, Giorgio Giannattasio
BACKGROUND: Reversible lymphocyte count reductions have occurred following daclizumab beta treatment for relapsing-remitting multiple sclerosis. OBJECTIVE: To analyse total and differential lymphocyte levels and relationship with infection status. METHODS: In DECIDE, blood samples were collected at 12-week intervals from daclizumab beta- ( n = 919) or intramuscular interferon beta-1a-treated ( n = 922) patients. Infections/serious infections were assessed proximate to grade 2/3 lymphopenia or low CD4(+)/CD8(+) T-cell counts...
September 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28906413/differences-in-clinical-features-observed-between-childhood-onset-versus-adult-onset-systemic-lupus-erythematosus-a-systematic-review-and-meta-analysis
#6
Pravesh Kumar Bundhun, Alka Kumari, Feng Huang
BACKGROUND: Systemic lupus erythematosus (SLE) affects people in childhood (childhood onset) or in adulthood (adult onset). Observational studies that have previously compared childhood-onset versus adult-onset SLE were often restricted to 1 ethnic group, or to a particular area, with a small sample size of patients. We aimed to systematically compare childhood-onset versus adult-onset SLE through a meta-analysis. METHODS: Electronic databases were searched for relevant publications comparing childhood-onset with adult-onset SLE...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28900067/-dimethyl-fumarate-in-multiple-sclerosis
#7
Masami Tanaka, Yuko Shimizu
At the end of 2016, dimethyl fumarate (DMF) was approved as the sixth disease-modifying drug for multiple sclerosis by the Pharmaceuticals and Medical Devices Agency of Japan. Two randomized, placebo-controlled, phase III studies (DEFINE and CONFIRM) showed beneficial effects in patients in Western countries, with relapsing-remitting multiple sclerosis (RRMS). Some of the benefits included a decreased annual relapse rate, inhibition of disease activity (shown using brain magnetic resonance imaging), and a decreased proportion of patients with confirmed disease progression...
September 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28894897/peptide-receptor-radionuclide-therapy-prrt-in-european-neuroendocrine-tumour-society-enets-grade-3-g3-neuroendocrine-neoplasia-nen-a-single-institution-retrospective-analysis
#8
Sue Ping Thang, Mei Sim Lung, Grace Kong, Michael S Hofman, Jason Callahan, Michael Michael, Rodney J Hicks
PURPOSE: Grade 3 NENs are aggressive tumours with poor prognosis. PRRT+/- radiosensitising chemotherapy is a potential treatment for disease with high somatostatin receptor (SSTR) expression without spatially discordant FDG-avid disease. We retrospectively evaluated the efficacy of PRRT in G3 NEN. METHODS: Kaplan-Meier estimation was used to determine progression-free survival (PFS) and overall survival (OS) defined from start of PRRT. Subgroup analysis was performed for patients with Ki-67 ≤ 55% and >55%...
September 12, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28894565/hematological-characteristics-of-yemeni-adults-and-children-with-visceral-leishmaniasis-could-eosinopenia-be-a-suspicion-index
#9
Jameel Al-Ghazaly, Waled Al-Dubai, Munasser Abdullah, Leila Al-Gharasi
BACKGROUND AND OBJECTIVES: Delay in the diagnosis of visceral leishmaniasis (VL) particularly in non-endemic areas is associated with higher mortality. In our experience, we found that marked bone marrow eosinopenia was a very frequent accompaniment of VL and might be a useful clue for the diagnosis, which indicates the opportunity for further morphological assessment. The aim of this study was to describe the hematological characteristics including peripheral blood and bone marrow findings of Yemeni adults and children with VL...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28888255/what-does-screening-newborns-for-t-cell-lymphopenia-find
#10
EDITORIAL
Sean A McGhee, Roger H Kobayashi
No abstract text is available yet for this article.
September 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28881832/the-novel-sphingosine-1-phosphate-receptors-antagonist-ad2900-affects-lymphocyte-activation-and-inhibits-t-cell-entry-into-the-lymph-nodes
#11
Jing Song, Arie Dagan, Zhanna Yakhtin, Shimon Gatt, Sean Riley, Hugh Rosen, Reuven Or, Osnat Almogi-Hazan
Sphingolipid derivatives play key roles in immune cell migration and function. Synthetic sphingolipid analogues are used as therapeutics to intervene various inflammatory and malignant conditions. We hypothesize that different analogs have different effects on immune cells and therefore can be used as treatment for specific diseases. This study examines the properties of the novel synthetic sphingolipid analog, AD2900, and its effects on immune cell activation and lymphocyte localization in homeostasis. AD2900 is an antagonist for all sphingosine-1-phosphate (S1P) receptors...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877956/organ-and-cell-specific-immune-responses-are-associated-with-the-outcomes-of-intracerebral-hemorrhage
#12
Jing Zhang, Kaibin Shi, Zhiguo Li, Minshu Li, Yujuan Han, Lei Wang, Zhecheng Zhang, Changlu Yu, Fang Zhang, Lijuan Song, Jing-Fei Dong, Antonio La Cava, Kevin N Sheth, Fu-Dong Shi
Severe brain injury significantly influences immune responses; however, the levels at which this influence occurs and which neurogenic pathways are involved are not well defined. Here, we used MRI to measure spleen volume and tissue diffusion changes in patients with intracerebral hemorrhage (ICH). We observed increased capillary exchange and spleen shrinkage by d 3 post-ICH, with recovery by d 14. The extent of spleen shrinkage was associated with brain hematoma size, and a reduced progression of perihematomal edema was observed in the presence of severe spleen shrinkage...
September 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28870611/safety-and-activity-of-microrna-loaded-minicells-in-patients-with-recurrent-malignant-pleural-mesothelioma-a-first-in-man-phase-1-open-label-dose-escalation-study
#13
Nico van Zandwijk, Nick Pavlakis, Steven C Kao, Anthony Linton, Michael J Boyer, Stephen Clarke, Yennie Huynh, Agata Chrzanowska, Michael J Fulham, Dale L Bailey, Wendy A Cooper, Leonard Kritharides, Lloyd Ridley, Scott T Pattison, Jennifer MacDiarmid, Himanshu Brahmbhatt, Glen Reid
BACKGROUND: TargomiRs are minicells (EnGeneIC Dream Vectors) loaded with miR-16-based mimic microRNA (miRNA) and targeted to EGFR that are designed to counteract the loss of the miR-15 and miR-16 family miRNAs, which is associated with unsuppressed tumour growth in preclinical models of malignant pleural mesothelioma. We aimed to assess the safety, optimal dosing, and activity of TargomiRs in patients with malignant pleural mesothelioma. METHODS: In this first-in-man, open-label, dose-escalation phase 1 trial at three major cancer centres in Sydney (NSW, Australia), we recruited adults (aged ≥18 years) with a confirmed diagnosis of malignant pleural mesothelioma, measurable disease, radiological signs of progression after previous chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, life expectancy of 3 months or more, immunohistochemical evidence of tumour EGFR expression, and adequate bone marrow, liver, and renal function...
September 1, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28870107/safety-and-efficacy-of-cladribine-tablets-in-patients-with-relapsing-remitting-multiple-sclerosis-results-from-the-randomized-extension-trial-of-the-clarity-study
#14
Gavin Giovannoni, Per Soelberg Sorensen, Stuart Cook, Kottil Rammohan, Peter Rieckmann, Giancarlo Comi, Fernando Dangond, Abidemi K Adeniji, Patrick Vermersch
BACKGROUND: In the 2-year CLARITY study, cladribine tablets significantly improved clinical and magnetic resonance imaging (MRI) outcomes (vs placebo) in patients with relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To assess the safety and efficacy of cladribine treatment in a 2-year Extension study. METHODS: In this 2-year Extension study, placebo recipients from CLARITY received cladribine 3.5 mg/kg; cladribine recipients were re-randomized 2:1 to cladribine 3...
August 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28869956/the-implications-of-recent-recommendations-for-managing-patients-with-psoriasis-treated-with-fumaric-acid-esters
#15
Catherine C Foley, Oonagh E Molloy, Aoife Lally, Brian Kirby
BACKGROUND/AIMS: Fumaric acid esters (FAEs) are a well-established efficacious systemic treatment for psoriasis. Recent recommendations from the European Medicines Agency suggest monitoring of full blood count every 4 weeks for the duration of therapy for psoriasis. The aim of our study was to assess the incidence of lymphopenia in patients taking FAEs and the impact of recent recommendations for our practice. METHODS: We reviewed 151 patients treated with FAEs for psoriasis between December 2013 and 2015...
September 5, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/28867533/-primary-intestinal-lymphangiectasia-waldmann-s-disease
#16
S Vignes, J Bellanger
Primary intestinal lymphangiectasia (PIL), Waldmann's disease, is a rare disorder of unknown etiology characterized by dilated intestinal lacteals leading to lymph leakage into the small-bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. The main symptom is bilateral lower limb edema. Edema may be moderate to severe including pleural effusion, pericarditis or ascites...
August 31, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28860594/sirt6-promotes-osteogenic-differentiation-of-mesenchymal-stem-cells-through-bmp-signaling
#17
Ping Zhang, Yunsong Liu, Yuejun Wang, Min Zhang, Longwei Lv, Xiao Zhang, Yongsheng Zhou
SIRT6 has been identified as an H3K9 deacetylase and a critical regulator of genome stability, telomere integrity, and metabolic homeostasis. Sirt6-deficient mice displayed dramatic phenotypes including profound lymphopenia, loss of subcutaneous fat, lordokyphosis and low bone marrow density. Here, we report that SIRT6 regulates osteogenic differentiation independent of its deacetylase activity in vitro. Further mechanistic studies showed that SIRT6 involves the cell fate determination by modulating bone morphogenetic protein (BMP) signaling...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28852031/infection-with-the-makona-variant-results-in-a-delayed-and-distinct-host-immune-response-compared-to-previous-ebola-virus-variants
#18
Krista Versteeg, Andrea R Menicucci, Courtney Woolsey, Chad E Mire, Joan B Geisbert, Robert W Cross, Krystle N Agans, Daniel Jeske, Ilhem Messaoudi, Thomas W Geisbert
Zaire Ebolavirus (ZEBOV) continues to pose a significant threat to human health as highlighted by the recent epidemic that originated in West Africa and the ongoing outbreak in the Democratic Republic of the Congo. Although the ZEBOV variant responsible for this epidemic (Makona) shares significant genetic similarity with previously identified variants (Kikwit and Mayinga), recent reports suggest slower disease progression in nonhuman primates. However, the pathogenesis caused by the new variant is not fully understood...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28846923/elevated-intrathymic-sphingosine-1-phosphate-promotes-thymus-involution-during-sepsis
#19
Laura Kuchler, Lisa K Sha, Annika K Giegerich, Tilo Knape, Carlo Angioni, Nerea Ferreirós, Martina V Schmidt, Andreas Weigert, Bernhard Brüne, Andreas von Knethen
Sepsis mouse models revealed thymus atrophy, characterised by decreased thymus weight and loss of thymocytes due to apoptosis. Mice suffered from lymphopenia, a lack of T cells in the periphery, which attenuates their ability to fight against recurring and secondary infections during sepsis progression. Key players in thymus atrophy are IL-6, which is directly involved in thymus involution, and the sphingosine-1-phosphate - sphingosine-1-phosphate receptor 1 signaling, influencing thymocytes emigration. In healthy individuals a sphingosine-1-phosphate (S1P) gradient from lymphoid organs to the circulatory system serves as signal for mature T cell egress...
August 25, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28846869/xlf-cernunnos-an-important-but-puzzling-participant-in-the-nonhomologous-end-joining-dna-repair-pathway
#20
REVIEW
Vijay Menon, Lawrence F Povirk
DNA double strand breaks (DSBs) are one of the most deleterious DNA lesions that promote cell death, genomic instability and carcinogenesis. The two major cellular mechanisms that repair DSBs are Nonhomologous End-Joining (NHEJ) and Homologous Recombination Repair (HRR). NHEJ is the predominant pathway, in which XLF (also called Cernunnos) is a key player. Patients with XLF mutation exhibit microcephaly, lymphopenia, and growth retardation, and are immunodeficient and radiosensitive. During NHEJ, XLF interacts with XRCC4-Ligase IV, stimulates its ligase activity, and forms DNA-binding filaments of alternating XLF and XRCC4 dimers that may serve to align broken DNA and promote ligation of noncomplementary ends...
August 18, 2017: DNA Repair
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