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Steroid insensitivity

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https://www.readbyqxmd.com/read/29928921/paucigranulocytic-asthma-the-uncoupling-of-airway-obstruction-from-inflammation
#1
Omar Tliba, Reynold A Panettieri
Among patients with asthma, heterogeneity exists regarding the pattern of airway inflammation and response to treatment, prompting the necessity of recognizing specific phenotypes. Based on the analysis of inflammatory cell count in induced sputum, patients with asthma can be classified in four unique phenotypes; eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma (PGA). PGA is an asthma phenotype with no evidence of elevated numbers of eosinophils or neutrophils in sputum or blood, and in which anti-inflammatory therapies are ineffective in controlling symptoms...
June 18, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29914889/repeated-allergen-exposure-in-a-j-mice-causes-steroid-insensitive-asthma-via-a-defect-in-glucocorticoid-receptor-bioavailability
#2
Magda F Serra, Amanda C Cotias, Camila R R Pão, Julio B Daleprane, Patricia B Jurgilas, Gina C Couto, Edna A Anjos-Valotta, Renato S B Cordeiro, Vinicius F Carvalho, Patricia M R Silva, Marco A Martins
The importance of developing new animal models to assess the pathogenesis of glucocorticoid (GC)-insensitive asthma has been stressed. Because of the asthma-prone background of A/J mice, we hypothesized that asthma changes in these animals would be or become resistant to GCs under repeated exposures to an allergen. A/J mice were challenged with OVA for 2 or 4 consecutive d, starting on day 19 postsensitization. Oral dexamethasone or inhaled budesonide were given 1 h before challenge, and analyses were done 24 h after the last challenge...
June 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29807066/male-rats-with-same-sex-preference-show-higher-immobility-in-the-forced-swim-test-but-similar-effects-of-fluoxetine-and-desipramine-than-males-that-prefer-females
#3
Alejandra Hernández, Alonso Fernández-Guasti
Sex preference in male rats is partly determined by the organizational action of estradiol. Thus, several paradigms have used aromatase inhibitors to manipulate sex preference. We recently showed that a subpopulation of male rats prenatally treated with letrozole (0.56 μg/kg, G10-G22), a non-steroidal third generation aromatase inhibitor, had same sex preference, female sexual behavior (including lordosis and proceptivity) and penile erections when exposed to other males. These males, in addition, displayed high levels of experimental anxiety in the plus maze test and were insensitive to the anxiogenic-like acute effect of FLX (10 mg/kg)...
May 25, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29742184/complex-regional-pain-syndrome-what-the-dermatologist-should-know
#4
Azam A Qureshi, Adam J Friedman
Reflex sympathetic dystrophy is a subtype of complex regional pain syndrome, a condition characterized by persistent post-injury extremity pain. Temperature and sweating changes, edema, mobility changes, and a variety of hair, nail, and skin sequelae have been described. Only 23 articles published since 1990 describe dermatologic changes in CRPS. Given this paucity of literature, we present a case to further elucidate cutaneous manifestations of CRPS. Our patient is a 52-year-old Caucasian woman with a 19-year history of reflex sympathetic dystrophy who has presented with several dermatologic complaints...
May 1, 2018: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29625381/transcriptomics-provides-mechanistic-indicators-of-mixture-toxicology-for-imx-101-and-imx-104-formulations-in-fathead-minnows-pimephales-promelas
#5
Kurt A Gust, Guilherme R Lotufo, Jacob K Stanley, Mitchell S Wilbanks, Pornsawan Chappell, Natalie D Barker
Within the US military, new insensitive munitions (IMs) are rapidly replacing conventional munitions improving safety from unintended detonation. Toxicity data for IM chemicals are expanding rapidly, however IM constituents are typically deployed in mixture formulations, and very little is known about their mixture toxicology. In the present study we sought to characterize the mixture effects and toxicology of the two predominant IM formulations IMX-101 and IMX-104 in acute (48 h) larval fathead minnow (Pimephales promelas) exposures...
June 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29604166/ravl1-an-upstream-component-of-brassinosteroid-signalling-and-biosynthesis-regulates-ethylene-signalling-via-activation-of-eil1-in-rice
#6
LETTER
Xiao Feng Zhu, De Peng Yuan, Chong Zhang, Tian Ya Li, Yuan Hu Xuan
No abstract text is available yet for this article.
March 31, 2018: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/29499168/diesel-exhaust-particles-up-regulate-interleukin-17a-expression-via-ros-nf-%C3%AE%C2%BAb-in-airway-epithelium
#7
Chih-Ming Weng, Meng-Jung Lee, Jung-Re He, Ming-Wei Chao, Chun-Hua Wang, Han-Pin Kuo
IL-17A is implicated in many aspects of pathogenesis of severe asthma, including inducing neutrophilic inflammation, airway hyperresponsiveness, steroid insensitivity and airway remodeling. Diesel exhaust particles (DEP) emission from vehicles has been shown to expand Th17 cells to increase IL-17A release that contributes to DEP-mediated exacerbation of asthma severity. It is not known whether non-immune cells in airways may also release IL-17A in response to DEP exposure. In this study, We found IL-17A expression was upregulated in the epithelium of severe allergic asthma patients from high road traffic pollution areas compared to those in low...
May 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29459726/the-systemin-receptor-syr1-enhances-resistance-of-tomato-against-herbivorous-insects
#8
Lei Wang, Elias Einig, Marilia Almeida-Trapp, Markus Albert, Judith Fliegmann, Axel Mithöfer, Hubert Kalbacher, Georg Felix
The discovery in tomato of systemin, the first plant peptide hormone1,2 , was a fundamental change for the concept of plant hormones. Numerous other peptides have since been shown to play regulatory roles in many aspects of the plant life, including growth, development, fertilization and interactions with symbiotic organisms3-6 . Systemin, an 18 amino acid peptide derived from a larger precursor protein 7 , was proposed to act as the spreading signal that triggers systemic defence responses observed in plants after wounding or attack by herbivores1,7,8 ...
March 2018: Nature Plants
https://www.readbyqxmd.com/read/29329424/brassinosteroids-regulate-pavement-cell-growth-by-mediating-bin2-induced-microtubule-stabilization
#9
Xiaolei Liu, Qin Yang, Yuan Wang, Linhai Wang, Ying Fu, Xuelu Wang
Brassinosteroids (BRs), a group of plant steroid hormones, play important roles in regulating plant development. The cytoskeleton also affects key developmental processes and a deficiency in BR biosynthesis or signaling leads to abnormal phenotypes similar to those of microtubule-defective mutants. However, how BRs regulate microtubule and cell morphology remains unknown. Here, using liquid chromatography-tandem mass spectrometry, we identified tubulin proteins that interact with Arabidopsis BRASSINOSTEROID INSENSITIVE2 (BIN2), a negative regulator of BR responses in plants...
January 10, 2018: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29315590/brassinosteroids-regulate-glucosinolate-biosynthesis-in-arabidopsis-thaliana
#10
Ji H Lee, Jeongyeo Lee, HyeRan Kim, Won B Chae, Sun-Ju Kim, Yong P Lim, Man-Ho Oh
Plants must constantly adjust their growth and defense responses to deal with the wide variety of stresses they encounter in their environment. Among phytohormones, brassinosteroids (BRs) are an important group of plant steroid hormones involved in numerous aspects of the plant lifecycle including growth, development and responses to various stresses including insect attacks. Here, we show that BRs regulate glucosinolate (GS) biosynthesis and function in insect herbivory. Preference tests and larval feeding experiments using the generalist herbivore, diamondback moth (Plutella xylostella), revealed that the larvae prefer to feed on Arabidopsis thaliana brassinosteroid insensitive 1 (bri1-5) plants over wild-type Ws-2 or BRI1-Flag (bri1-5 background) transgenic plants, which results in an increase in larval weight...
January 13, 2018: Physiologia Plantarum
https://www.readbyqxmd.com/read/29288381/modulation-of-the-il-23-il-17-axis-by-fenofibrate-ameliorates-the-ovalbumin-lipopolysaccharide-induced-airway-inflammation-and-bronchial-asthma-in-rats
#11
Samah M Elaidy, Soha S Essawy, Mona A Hussain, Mohamed K El-Kherbetawy, Eman R Hamed
The overlapping between asthmatic subtypes, including both CD4+ T helper (TH)2 and TH17 cells, is found in the natural course of allergic asthma, especially in exacerbations and severe and insensitive forms to steroids, which are in need of new molecular therapies. In the TH2-subset mediated asthma, fenofibrate displays therapeutic promises, besides evidenced therapeutic effects on TH17-mediated colitis and myocarditis. Therefore, the effects of fenofibrate versus dexamethasone on IL-23/IL-17 axis in ovalbumin (OVA)/lipopolysaccharide (LPS)-induced airway inflammation and bronchial asthma in rats were explored...
March 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29233147/neutrophil-extracellular-traps-are-downregulated-by-glucocorticosteroids-in-lungs-in-an-equine-model-of-asthma
#12
Amandine Vargas, Roxane Boivin, Patricia Cano, Yoana Murcia, Isabelle Bazin, Jean-Pierre Lavoie
BACKGROUND: Severe neutrophilic asthma is poorly responsive to glucocorticosteroids (GC). Neutrophil extracellular traps (NETs) within the lungs have been associated with the severity of airway obstruction and inflammation in asthma, and were found to be unaffected by GC in vitro. As IL-17 is overexpressed in neutrophilic asthma and contributes to steroid insensitivity in different cell types, we hypothesized that NETs formation in asthmatic airways would be resistant to GC through an IL-17 mediated pathway...
December 12, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29223875/snakes-exhibit-tissue-specific-variation-in-cardiotonic-steroid-sensitivity-of-na-k-atpase
#13
Shabnam Mohammadi, Georg Petschenka, Susannah S French, Akira Mori, Alan H Savitzky
Toads are among several groups of organisms chemically defended with lethal concentrations of cardiotonic steroids. As a result, most predators that prey on amphibians avoid toads. However, several species of snakes have gained resistance-conferring mutations of Na+ /K+ -ATPase, the molecular target of cardiotonic steroids, and can feed on toads readily. Despite recent advances in our understanding of this adaptation at the genetic level, we have lacked functional evidence for how mutations of Na+ /K+ -ATPase account for cardiotonic steroid resistance in snake tissues...
March 2018: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29051026/mutational-analysis-of-the-androgen-receptor-nr3c4-gene-in-patients-with-46-xy-dsd
#14
L Ramos, B Chávez, L Mares, E Valdés, F Vilchis
Androgen insensitivity syndrome (AIS) is an X-linked disorder caused by mutations in the NR3C4 gene, which encodes the androgen receptor (AR). In this study, we performed mutational analyses to identify AR molecular defects, in individuals with 46,XY disorders of sex development (46,XY DSD) and a presumptive diagnosis of AIS. Eighteen different gene mutations, including seven previously unreported new variants, were detected in 26 unrelated cases. These included two deletion mutations (P49fs*185 and E308f*320) in exon 1 and five substitution mutations (p...
January 30, 2018: Gene
https://www.readbyqxmd.com/read/29046359/androgens-trigger-different-growth-responses-in-genetically-identical-human-hair-follicles-in-organ-culture-that-reflect-their-epigenetic-diversity-in-life
#15
Benjamin H Miranda, Matthew R Charlesworth, Desmond J Tobin, David T Sharpe, Valerie A Randall
Male sex hormones-androgens-regulate male physique development. Without androgen signaling, genetic males appear female. During puberty, increasing androgens harness the hair follicle's unique regenerative ability to replace many tiny vellus hairs with larger, darker terminal hairs ( e.g., beard). Follicle response is epigenetically varied: some remain unaffected ( e.g., eyelashes) or are inhibited, causing balding. How sex steroid hormones alter such developmental processes is unclear, despite high incidences of hormone-driven cancer, hirsutism, and alopecia...
February 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28949385/effects-of-testosterone-and-17%C3%AE-%C3%A2-estradiol-on-angiotensin%C3%A2-induced-changes-in-tyrosine-kinase-activity-in-the-androgen%C3%A2-independent-human-prostate-cancer-cell-line-du145
#16
Kamila Domińska, Antoni Kowalski, Tomasz Ochędalski, Elżbieta Rębas
Angiotensin II (AngII), the main peptide of the renin‑angiotensin system (RAS), is involved in the proliferation of different types of cells, normal and pathological as well. The protein tyrosine kinases (PTKs) play an important role in the growth, differentiation and apoptosis of cells. AngII action depends on the hormonal milieu of the cell, and on sex steroid influence. Angiotensin 1‑7 (Ang1‑7), metabolite of AngII, shows opposite action to AngII in cells. The present study aimed to examine the influence of 17β‑estradiol and testosterone on AngII and Ang1‑7 action on PTK activity in androgen‑independent humane prostate cancer cell line DU145...
September 25, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28948813/peripheral-sensitivity-to-steroids-revisited
#17
R Hampl, K Vondra
Resistance to steroid hormones presents a serious problem with respect to their mass use in therapy. It may be caused genetically by mutation of genes involved in hormonal signaling, not only steroid receptors, but also other players in the signaling cascade as co-regulators and other nuclear factors, mediating the hormone-born signal. Another possibility is acquired resistance which may develop under long-term steroid treatment, of which a particular case is down regulation of the receptors. In the review recent knowledge is summarized on the mechanism of main steroid hormone action, pointing to already proven or potential sites causing steroid resistance...
September 26, 2017: Physiological Research
https://www.readbyqxmd.com/read/28933920/multitissue-transcriptomics-delineates-the-diversity-of-airway-t-cell-functions-in-asthma
#18
Akul Singhania, Joshua C Wallington, Caroline G Smith, Daniel Horowitz, Karl J Staples, Peter H Howarth, Stephan D Gadola, Ratko Djukanović, Christopher H Woelk, Timothy S C Hinks
Asthma arises from the complex interplay of inflammatory pathways in diverse cell types and tissues. We sought to undertake a comprehensive transcriptomic assessment of the epithelium and airway T cells that remain understudied in asthma and investigate interactions between multiple cells and tissues. Epithelial brushings and flow-sorted CD3+ T cells from sputum and BAL were obtained from healthy subjects (n = 19) and patients with asthma (mild, moderate, and severe asthma; n = 46). Gene expression was assessed using Affymetrix HT HG-U133+ PM GeneChips, and results were validated by real-time quantitative PCR...
February 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28851976/linoleic-acid-metabolite-leads-to-steroid-resistant-asthma-features-partially-through-nf-%C3%AE%C2%BAb
#19
Lipsa Panda, Atish Gheware, Rakhshinda Rehman, Manish K Yadav, B S Jayaraj, SubbaRao V Madhunapantula, Padukudru Anand Mahesh, Balaram Ghosh, Anurag Agrawal, Ulaganathan Mabalirajan
Studies have highlighted the role of nutritional and metabolic modulators in asthma pathobiology. Steroid resistance is an important clinical problem in asthma but lacks good experimental models. Linoleic acid, a polyunsaturated fatty acid, has been linked to asthma and glucocorticoid sensitivity. Its 12/15-lipoxygenase metabolite, 13-S-hydroxyoctadecadienoic acid (HODE) induces mitochondrial dysfunction, with severe airway obstruction and neutrophilic airway inflammation. Here we show that HODE administration leads to steroid unresponsiveness in an otherwise steroid responsive model of allergic airway inflammation (AAI)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28755528/tissue-kallikrein-related-peptidase-4-klk4-a-novel-biomarker-in-triple-negative-breast-cancer
#20
Feng Yang, Michaela Aubele, Axel Walch, Eva Gross, Rudolf Napieralski, Shuo Zhao, Nancy Ahmed, Marion Kiechle, Ute Reuning, Julia Dorn, Fred Sweep, Viktor Magdolen, Manfred Schmitt
Triple-negative breast cancer (TNBC), lacking the steroid hormone receptors ER and PR and the oncoprotein HER2, is characterized by its aggressive pattern and insensitivity to endocrine and HER2-directed therapy. Human kallikrein-related peptidases KLK1-15 provide a rich source of serine protease-type biomarkers associated with tumor growth and cancer progression for a variety of malignant diseases. In this study, recombinant KLK4 protein was generated and affinity-purified KLK4-directed polyclonal antibody pAb587 established to allow localization of KLK4 protein expression in tumor cell lines and archived formalin-fixed, paraffin-embedded TNBC tumor tissue specimens...
September 26, 2017: Biological Chemistry
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