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https://www.readbyqxmd.com/read/29775622/clinicopathological-analysis-of-immunohistochemical-expression-of-retinoic-acid-related-orphan-receptor-%C3%AE-t-in-peripheral-t-cell-lymphoma-not-otherwise-specified
#1
Eriko Yanagida, Hiroaki Miyoshi, Keisuke Kawamoto, Kazutaka Nakashima, Kotaro Matsuda, Kyohei Yamada, Reiji Muto, Koji Nagafuji, Masao Seto, Koichi Ohshima
Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is cytologically and phenotypically heterogeneous. Retinoic acid-related orphan receptor-γt (RORγt) is a transcription factor that regulates the differentiation of naïve CD4+ helper T-cells to Th17 cells. In the present study, we immunohistochemically confirmed the expression of RORγt in PTCL-NOS. Pathological and clinical investigations were performed for 170 cases of PTCL-NOS. RORγt-positive cases accounted for 17.6% (30/170) of the total cases and they showed a significantly higher frequency of CD8 positivity (P=...
May 15, 2018: Human Pathology
https://www.readbyqxmd.com/read/29774027/clinical-remission-of-sight-threatening-non-infectious-uveitis-is-characterized-by-an-upregulation-of-peripheral-t-regulatory-cell-polarized-towards-t-bet-and-tigit
#2
Rose M Gilbert, Xiaozhe Zhang, Robert D Sampson, Michael R Ehrenstein, Dao X Nguyen, Mahid Chaudhry, Charles Mein, Nadiya Mahmud, Grazyna Galatowicz, Oren Tomkins-Netzer, Virginia L Calder, Sue Lightman
Background: Non-infectious uveitis can cause chronic relapsing and remitting ocular inflammation, which may require high dose systemic immunosuppression to prevent severe sight loss. It has been classically described as an autoimmune disease, mediated by pro-inflammatory Th1 and Th17 T-cell subsets. Studies suggest that natural immunosuppressive CD4+ CD25+ FoxP3+ T-regulatory cells (Tregs) are involved in resolution of inflammation and may be involved in the maintenance of clinical remission...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29772059/the-orphan-g-protein-coupled-receptor-75-signaling-is-activated-by-the-chemokine-ccl5
#3
Simona Dedoni, Lee A Campbell, Brandon K Harvey, Valeria Avdoshina, Italo Mocchetti
The chemokine CCL5 prevents neuronal cell death mediated both by amyloid β, as well as the human immunodeficiency virus (HIV) viral proteins gp120 and Tat. Because CCL5 binds to CCR5, CCR3 and/or CCR1 receptors, it is unclear which of these receptors plays a role in neuroprotection. Indeed, CCL5 also has neuroprotective activity in cells lacking these receptors. CCL5 may bind to a G protein-coupled receptor 75 (GPR75), which encodes for a 540 amino-acid orphan receptor of the Gqα family. In this study, we have used SH-SY5Y human neuroblastoma cells to characterize whether CCL5 could activate a Gq signaling through GPR75...
May 17, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29771310/fingolimod-phosphate-inhibits-astrocyte-inflammatory-activity-in-mucolipidosis-iv
#4
Laura Weinstock, Amanda M Furness, Shawn Herron, Sierra S Smith, Sitara Sankar, Samantha G DeRosa, Dadi Gao, Molly E Mepyans, Anna Scotto Rosato, Diego L Medina, Ayelet Vardi, Natalia S Ferreira, Soo Min Cho, Anthony H Futerman, Susan A Slaugenhaupt, Levi B Wood, Yulia Grishchuk
Mucolipidosis IV (MLIV) is an orphan neurodevelopmental disease that causes severe neurologic dysfunction and loss of vision. Currently there is no therapy for MLIV. It is caused by loss of function of the lysosomal channel mucolipin-1, also known as TRPML1. Knockout of the Mcoln1 gene in a mouse model mirrors clinical and neuropathological signs in humans. Using this model, we previously observed robust activation of microglia and astrocytes in early symptomatic stages of disease. Here we investigate the consequence of mucolipin-1 loss on astrocyte inflammatory activation in vivo and in vitro and apply a pharmacological approach to restore Mcoln1-/- astrocyte homeostasis using a clinically approved immunomodulator, fingolimod...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29769519/optical-functionalization-of-human-class-a-orphan-g-protein-coupled-receptors
#5
Maurizio Morri, Inmaculada Sanchez-Romero, Alexandra-Madelaine Tichy, Stephanie Kainrath, Elliot J Gerrard, Priscila P Hirschfeld, Jan Schwarz, Harald Janovjak
G-protein-coupled receptors (GPCRs) form the largest receptor family, relay environmental stimuli to changes in cell behavior and represent prime drug targets. Many GPCRs are classified as orphan receptors because of the limited knowledge on their ligands and coupling to cellular signaling machineries. Here, we engineer a library of 63 chimeric receptors that contain the signaling domains of human orphan and understudied GPCRs functionally linked to the light-sensing domain of rhodopsin. Upon stimulation with visible light, we identify activation of canonical cell signaling pathways, including cAMP-, Ca2+ -, MAPK/ERK-, and Rho-dependent pathways, downstream of the engineered receptors...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29769380/pneumococcal-metabolic-adaptation-and-colonization-are-regulated-by-the-two-component-regulatory-system-08
#6
Alejandro Gómez-Mejia, Gustavo Gámez, Stephanie Hirschmann, Viktor Kluger, Hermann Rath, Sebastian Böhm, Franziska Voss, Niamatullah Kakar, Lothar Petruschka, Uwe Völker, Reinhold Brückner, Ulrike Mäder, Sven Hammerschmidt
Streptococcus pneumoniae two-component regulatory systems (TCS) enable adaptation and ensure its maintenance in host environments. This study deciphers the impact of TCS08 on pneumococcal gene expression and its role in metabolic and pathophysiological processes. Transcriptome analysis and real-time PCR demonstrated a regulatory effect of TCS08 on genes involved mainly in environmental information processing, intermediary metabolism, and colonization by S. pneumoniae D39 and TIGR4. Striking examples are genes for fatty acid biosynthesis, genes of the arginine deiminase system, and the psa operon encoding the manganese ABC transport system...
June 27, 2018: MSphere
https://www.readbyqxmd.com/read/29767233/potential-role-of-cyclin-f-mrna-expression-in-the-survival-of-skin-melanoma-patients-comprehensive-analysis-of-the-pathways-altered-due-to-cyclin-f-upregulation
#7
Maciej Gagat, Adrian Krajewski, Dariusz Grzanka, Alina Grzanka
Cyclin F is a part of the Skp, Cullin, F-box containing ligase complex. The activity of cyclin F includes cell cycle control, centrosome duplication and response to DNA damage. The cyclin F expression pattern is very similar to cyclin A, but cyclin F is an orphan cyclin without its cyclin-dependent kinase partner. There is little evidence concerning the role of cyclin F in cancer. In the present study, for the first time, we present analysis from The Cancer Genome Atlas (TCGA) data in the context of expression of cyclin F mRNA in melanoma patients...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29765774/how-shall-we-treat-early-triple-negative-breast-cancer-tnbc-from-the-current-standard-to-upcoming-immuno-molecular-strategies
#8
REVIEW
Ji Hyun Park, Jin-Hee Ahn, Sung-Bae Kim
Triple-negative breast cancer (TNBC) is a long-lasting orphan disease in terms of little therapeutic progress during the past several decades and still the standard of care remains chemotherapy. Experimental discovery of molecular signatures including the 'BRCAness' highlighted the innate heterogeneity of TNBC, generating the diversity of TNBC phenotypes. As it contributes to enhancing genomic instability, it has widened the therapeutic spectrum of TNBC. In particular, unusual sensitivity to DNA damaging agents was denoted in patients with BRCA deficiency, suggesting therapeutic benefit from platinum and poly(ADP-ribose) polymerase inhibitors...
2018: ESMO Open
https://www.readbyqxmd.com/read/29765641/combined-morphological-and-phylogenomic-re-examination-of-malawimonads-a-critical-taxon-for-inferring-the-evolutionary-history-of-eukaryotes
#9
Aaron A Heiss, Martin Kolisko, Fleming Ekelund, Matthew W Brown, Andrew J Roger, Alastair G B Simpson
Modern syntheses of eukaryote diversity assign almost all taxa to one of three groups: Amorphea, Diaphoretickes and Excavata (comprising Discoba and Metamonada). The most glaring exception is Malawimonadidae, a group of small heterotrophic flagellates that resemble Excavata by morphology, but branch with Amorphea in most phylogenomic analyses. However, just one malawimonad, Malawimonas jakobiformis , has been studied with both morphological and molecular-phylogenetic approaches, raising the spectre of interpretation errors and phylogenetic artefacts from low taxon sampling...
April 2018: Royal Society Open Science
https://www.readbyqxmd.com/read/29764667/bacterial-pathogens-of-bees
#10
REVIEW
Anne Fünfhaus, Julia Ebeling, Elke Genersch
Pollination is an indispensable ecosystem service provided by many insects, especially by wild and managed bee species. Hence, reports on large scale honey bee colony losses and on population declines of many wild bees were alarming and resulted in increased awareness of the importance of bee health and increased interest in bee pathogens. To serve this interest, this review will give a comprehensive overview on bacterial bee pathogens by covering not only the famous pathogens (Paenibacillus larvae, Melissococcus plutonius), but also the orphan pathogens which have largely been neglected by the scientific community so far (spiroplasmas) and the pathogens which were only recently discovered as being pathogenic to bees (Serratia marcescens, Lysinibacillus sphaericus)...
April 2018: Current Opinion in Insect Science
https://www.readbyqxmd.com/read/29757590/imbalance-of-peripheral-blood-t-helper-type-17-responses-in-patients-with-vitiligo
#11
Farinaz Behfarjam, Parvine Mansouri, Zohreh Jadali
There is growing evidence to suggest that Th cells play pivotal roles in a variety of chronic inflammatory diseases, including vitiligo. However, the exact role of different subsets of Th cells in the pathogenesis of vitiligo is still a question. The purpose of present study was to determine the mRNA expression level of Th17 master transcription factor retinoic acid receptor-related orphan receptors gamma (RORɣt) and cytokine mRNA and protein expression profiles of Th17 cells. 22 patients with vitiligo and 22 normal subjects were enrolled in the study...
April 2018: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29754637/new-molecular-targets-for-treatment-of-cushing-s-disease
#12
REVIEW
Elizabeth Foulkes, John Newell-Price
Despite the best outcomes from trans-sphenoidal surgery, approximately one-third of patients with Cushing's disease will need medical therapy. Current treatments have drawbacks and there is a clear clinical need for new therapies. Recent understanding of molecular pathways leading to excess ACTH secretion has identified key components that may be targeted with the aim to provide novel effective treatment for this devastating disease. These include testicular orphan nuclear receptor 4, heat shock protein 90, and epidermal growth factor receptor...
June 2018: Endocrinology and Metabolism Clinics of North America
https://www.readbyqxmd.com/read/29754010/influence-of-brain-plasmalogen-changes-on-gonadotropin-secretion-from-the-cultured-bovine-anterior-pituitary-cells
#13
O Kereilwe, K Pandey, H Kadokawa
We recently discovered that the orphan G-protein-coupled receptor (GPR) 61 colocalized with GnRH receptors (GnRHRs) on the surface of most of bovine gonadotrophs. A recent study suggested that ethanolamine plasmalogen (PI) is a ligand for GPR61 in mouse neuroblastoma. Therefore, this study evaluated the hypothesis that PI alters LH and FSH secretion from cultured bovine anterior pituitary (AP) cells. We prepared bovine AP cells from postpubertal heifers (26 mo old) and cultured the cells for 3.5 d. We treated the cells with increasing concentrations (0, 5, 50, 500, 5,000, 50,000, or 500,000 pg/mL) of phosphoethanolamine PI (PEPI) extracted from the bovine brain, or l-α-lysophosphatidylethanolamine PI (LEPI) extracted from the bovine brain, for 5 min before either no treatment or GnRH stimulation...
April 10, 2018: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29753352/patient-access-to-medicines-for-rare-diseases-in-european-countries
#14
Andreja Detiček, Igor Locatelli, Mitja Kos
BACKGROUND: The number of authorized orphan and non-orphan medicines for rare diseases has increased in Europe. Patient access to these medicines is affected by high costs, weak efficacy/safety evidence, and societal value. European health care systems must determine whether paying for expensive treatments for only a few patients is sustainable. OBJECTIVES: This study aimed to evaluate patient access to orphan and non-orphan medicines for rare diseases in 22 European countries during 2005 to 2014...
May 2018: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/29753351/evaluating-and-valuing-drugs-for-rare-conditions-no-easy-answers
#15
Daniel A Ollendorf, Richard H Chapman, Steven D Pearson
We find ourselves in an era of unprecedented growth in the development and use of so-called "orphan" drugs to treat rare diseases, which are poised to represent more than one-fifth of pharmaceutical expenditures by 2022. This widespread use has been facilitated by legislative and regulatory incentives in both the United States and abroad, yet US payers and health systems have not yet made a concerted effort to understand whether and how rare diseases require special considerations on their part and how to adapt traditional methods of health technology assessment and economic evaluation to accommodate these situations...
May 2018: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/29753350/societal-preferences-for-funding-orphan-drugs-in-the-united-kingdom-an-application-of-person-trade-off-and-discrete-choice-experiment-methods
#16
Siobhan M Bourke, Catrin O Plumpton, Dyfrig A Hughes
BACKGROUND: It is unclear whether UK National Health Service (NHS) policies for orphan drugs, which permit funding of non-cost-effective treatments, reflect societal preferences. METHODS: We conducted person trade-off (PTO) and discrete choice experiment (DCE) among 3950 adults selected to be representative of the UK general population. Experimental design was informed by surveys of patients affected by rare diseases, their caregivers, health care staff, and policymakers...
May 2018: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/29753348/budgetary-impact-and-cost-drivers-of-drugs-for-rare-and-ultrarare-diseases
#17
REVIEW
Michael Schlander, Charalabos-Markos Dintsios, Afschin Gandjour
OBJECTIVES: To review recent studies reporting health care expenditures (budgetary impact) for orphan medicinal products (OMPs) in Europe and to contribute to our understanding of the cost drivers of nononcological OMPs by means of an empirical analysis in Germany. METHODS: A systematic search for relevant studies on rare diseases was conducted in PubMed and Embase (until December 2016). In addition, annual treatment costs of nononcological OMPs in Germany were analyzed with respect to five explanatory variables: total prevalence of disease, prevalence with added benefit, availability of alternative treatments for the same indication, extent/probability of treatment benefit, and evidence for a treatment effect on mortality...
May 2018: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/29753347/economic-modeling-considerations-for-rare-diseases
#18
Isobel Pearson, Ben Rothwell, Andrew Olaye, Christopher Knight
OBJECTIVES: To identify challenges that affect the feasibility and rigor of economic models in rare diseases and strategies that manufacturers have employed in health technology assessment submissions to demonstrate the value of new orphan products that have limited study data. METHODS: Targeted reviews of PubMed, the National Institute for Health and Care Excellence's (NICE's) Highly Specialised Technologies (HST), and the Scottish Medicines Consortium's (SMC's) ultra-orphan submissions were performed...
May 2018: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/29749556/andrographolide-affects-th1-th2-th17-responses-of-peripheral-blood-mononuclear-cells-from-ulcerative-colitis-patients
#19
Qin Zhu, Peifen Zheng, Jianying Zhou, Xinyu Chen, Yuliang Feng, Weifeng Wang, Feng Zhou, Qiaona He
Ulcerative colitis (UC) is a chronic, idiopathic, inflammatory bowel disease of the colon. T cell responses have been associated with the pathology of UC. Andrographis paniculata (AP) extract has been previously reported as an effective treatment of UC. The present study aimed to explore the effects of andrographolide, the primary active component of AP, on the T cell responses of patients with UC. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with UC and treated with various concentrations of andrographolide (0, 10, 20 and 30 µg/ml)...
May 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29748645/transcriptome-and-co-expression-network-analyses-identify-key-genes-regulating-nitrogen-use-efficiency-in-brassica-juncea-l
#20
Parul Goel, Nitesh Kumar Sharma, Monika Bhuria, Vishal Sharma, Rohit Chauhan, Shivalika Pathania, Mohit Kumar Swarnkar, Vandna Chawla, Vishal Acharya, Ravi Shankar, Anil Kumar Singh
Nitrate is the main source of inorganic nitrogen for plants, which also act as signaling molecule. Present study was aimed to understand nitrate regulatory mechanism in Brassica juncea cultivars, with contrasting nitrogen-use-efficiency (NUE) viz. Pusa Bold (PB, high-NUE) and Pusa Jai Kisan (PJK, low-NUE), employing RNA-seq approach. A total of 4031, 3874 and 3667 genes in PB and 2982, 2481 and 2843 genes in PJK were differentially expressed in response to early, low (0.25 mM KNO3 ), medium (2 mM KNO3 ) and high (4 mM KNO3 ) nitrate treatments, respectively, as compared to control (0 mM KNO3 )...
May 10, 2018: Scientific Reports
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