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Steroid insensitivity

Vidya Ramachandraiah, Wilbert Aronow, Dipak Chandy
Sarcoidosis is a multisystem disease characterized by the presence of noncaseating granulomas, the exact etiology of which is yet to be determined. Pulmonary involvement occurs in the majority of patients and its severity ranges from asymptomatic involvement of mediastinal lymph nodes to progressive pulmonary fibrosis and chronic respiratory failure that is insensitive to treatment. Diagnosis of pulmonary sarcoidosis requires a compatible clinical picture supported by radiologic and pathologic data. A recent development in establishing the diagnosis of pulmonary sarcoidosis is endobronchial ultrasound that increases the yield of transbronchial needle aspiration of hilar and/or mediastinal lymph nodes...
October 21, 2016: Postgraduate Medicine
Keiko Yamada, Junhui Yuan, Tomoo Mano, Hiroshi Takashima, Masahiko Shibata
BACKGROUND: Hereditary sensory and autonomic neuropathy (HSAN) type II with WNK1/HSN2 gene mutation is a rare disease characterized by early-onset demyelination sensory loss and skin ulceration. To the best of our knowledge, no cases of an autonomic disorder have been reported clearly in a patient with WNK/HSN2 gene mutation and only one case of a Japanese patient with the WNK/HSN2 gene mutation of HSAN type II was previously reported. CASE PRESENTATION: Here we describe a 54-year-old woman who had an early childhood onset of insensitivity to pain; superficial, vibration, and proprioception sensation disturbances; and several symptoms of autonomic failure (e...
October 21, 2016: BMC Neurology
Peter A Bos
Variation in the quality of parental care has a tremendous impact on a child's social-emotional development. Research investigating the predictors of this variability in human caregiving behavior has mostly focused on learning mechanisms. Evidence is currently accumulating for the complementary underlying role of steroid hormones and neuropeptides. An overview is provided of the hormones and neuropeptides relevant for human caregiving behavior. Then the developmental factors are described that stimulate variability in sensitivity to these hormones and neuropeptides, which may result in variability in the behavioral repertoire of caregiving...
October 20, 2016: Development and Psychopathology
Cassandra E Deering-Rice, Chris Stockmann, Erin G Romero, Zhenyu Lu, Darien Shapiro, Brian L Stone, Bernhard Fassl, Flory Nkoy, Derek A Uchida, Robert M Ward, John M Veranth, Christopher A Reilly
Transient receptor potential (TRP) channels are activated by environmental particulate materials. We hypothesized that polymorphic variants of TRPV1 would be uniquely responsive to insoluble coal fly ash compared to the prototypical soluble agonist capsaicin. Furthermore, these changes would manifest as differences in lung cell responses to these agonists and perhaps correlate with changes in asthma symptom control. The TRPV1 I315M and T469I variants were more responsive to capsaicin and coal fly ash. The I585V variant was less responsive to coal fly ash particles, due to reduced translation of protein and an apparent role for I585 in activation by particles...
October 7, 2016: Journal of Biological Chemistry
Qian-Feng Li, Min Xiong, Peng Xu, Li-Chun Huang, Chang-Quan Zhang, Qiao-Quan Liu
Brassinosteroids (BRs), essential plant-specific steroidal hormones, function in a wide spectrum of plant growth and development events, including seed germination. Rice is not only a monocotyledonous model plant but also one of the most important staple food crops of human beings. Rice seed germination is a decisive event for the next-generation of plant growth and successful seed germination is critical for rice yield. However, little is known about the molecular mechanisms on how BR modulates seed germination in rice...
October 5, 2016: Scientific Reports
Lara Ravanetti, Annemiek Dijkhuis, Yanaika S Sabogal Pineros, Suzanne M Bal, Barbara S Dierdorp, Tamara Dekker, Adrian Logiantara, Ian M Adcock, Navin L Rao, Louis Boon, Gino Villetti, Peter J Sterk, Fabrizio Facchinetti, René Lutter
BACKGROUND: Acute worsening of asthma symptoms (exacerbation) is predominantly triggered by respiratory viruses, with influenza causing the most severe exacerbations. The lack of an adequate animal model hampers mechanistic insight and the development of new therapeutics. AIM: We developed and characterized a robust, consistent and reproducible mouse model of severe exacerbation of chronic allergic asthma. METHODS: Chronic allergic airway inflammation was induced following a house dust mite (HDM)-sensitization protocol...
October 3, 2016: Allergy
Stephen Wilson, Jianfei Qi, Fabian V Filipp
Sequence motifs are short, recurring patterns in DNA that can mediate sequence-specific binding for proteins such as transcription factors or DNA modifying enzymes. The androgen response element (ARE) is a palindromic, dihexameric motif present in promoters or enhancers of genes targeted by the androgen receptor (AR). Using chromatin immunoprecipitation sequencing (ChIP-Seq) we refined AR-binding and AREs at a genome-scale in androgen-insensitive and androgen-responsive prostate cancer cell lines. Model-based searches identified more than 120,000 ChIP-Seq motifs allowing for expansion and refinement of the ARE...
2016: Scientific Reports
Richard Y Kim, Jay C Horvat, James W Pinkerton, Malcolm R Starkey, Ama T Essilfie, Jemma R Mayall, Prema M Nair, Nicole G Hansbro, Bernadette Jones, Tatt Jhong Haw, Krishna P Sunkara, Thi Hiep Nguyen, Andrew G Jarnicki, Simon Keely, Joerg Mattes, Ian M Adcock, Paul S Foster, Philip M Hansbro
BACKGROUND: Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The mechanisms that underpin infection-induced, severe steroid-insensitive asthma can be elucidated by using mouse models of disease...
June 10, 2016: Journal of Allergy and Clinical Immunology
Reynold A Panettieri
Although 2 T-helper type 2 inflammation evokes airway hyperresponsiveness and narrowing, neutrophilic or pauci-immune asthma accounts for significant asthma morbidity. Viruses, toxicants, environmental tobacco smoke exposure, and bacterial infections induce asthma exacerbations mediated by neutrophilic inflammation or by structural cell (pauci-immune) mechanisms. Therapeutic challenges exist in the management of neutrophilic and pauci-immune phenotypes because both syndromes manifest steroid insensitivity. The recognition that neutrophil subsets exist and their functions are unique poses exciting opportunities to develop precise therapies...
August 2016: Immunology and Allergy Clinics of North America
Yun Song, Ping Yu, Juan-Juan Lu, Hao-Zhong Lu, Liang Zhu, Zhi-Hua Yu, Hong-Zhuan Chen, Yong-Yao Cui
Steroid insensitivity has been commonly found in chronic obstructive pulmonary disease (COPD) patients, which is mediated by the reduction of histone deacetylase (HDAC) 2. Here we aimed to establish a steroid resistant model on experimental COPD rats and evaluate the effect of carbocisteine (S-CMC), a mucoactive drug. Exposure to cigarette smoke (CS) caused marked pathological features of COPD which are insensitive to DEX associated with the down-regulation of HDAC2 expression/activity. The DEX insensitivity observed in COPD featured rats was improved by S-CMC in the aspects of inhibiting chronic lung inflammation (total and differential inflammatory cell counts, inflammatory cytokines release and inflammatory cells infiltration); ameliorating airway remodeling (thickness of airway epithelium and smooth muscle, airway fibrosis, and the level of α-SMA and TGF-β1); improving emphysema (emphysema index D2, level of MMP-9 in BALF and the expression of alpha-1 antitrypsin) and preventing impairments of lung function (PEF, IP and IP-slope)...
August 2016: Pulmonary Pharmacology & Therapeutics
Eric B Brandt, Gurjit K Khurana Hershey
No abstract text is available yet for this article.
September 2016: Journal of Allergy and Clinical Immunology
D Chesnoy-Marchais
In hypoglossal motoneurons, a sustained anionic current, sensitive to a blocker of ρ-containing GABA receptors, (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) and insensitive to bicuculline, was previously shown to be activated by gabazine. In order to better characterize the receptors involved, the sensitivity of this atypical response to pentobarbital (30μM), allopregnanolone (0.3μM) and midazolam (0.5μM) was first investigated. Pentobarbital potentiated the response, whereas the steroid and the benzodiazepine were ineffective...
August 25, 2016: Neuroscience
Justin R Buland, Karla J Wasserloos, Vladimir A Tyurin, Yulia Y Tyurina, Andrew A Amoscato, Rama K Mallampalli, Bill B Chen, Jing Zhao, Yutong Zhao, Solomon Ofori-Acquah, Valerian E Kagan, Bruce R Pitt
We (66) have previously described an NSAID-insensitive intramitochondrial biosynthetic pathway involving oxidation of the polyunsaturated mitochondrial phospholipid, cardiolipin (CL), followed by hydrolysis [by calcium-independent mitochondrial calcium-independent phospholipase A2-γ (iPLA2γ)] of oxidized CL (CLox), leading to the formation of lysoCL and oxygenated octadecadienoic metabolites. We now describe a model system utilizing oxidative lipidomics/mass spectrometry and bioassays on cultured bovine pulmonary artery endothelial cells (BPAECs) to assess the impact of CLox that we show, in vivo, can be released to the extracellular space and may be hydrolyzed by lipoprotein-associated PLA2 (Lp-PLA2)...
August 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Nicoletta Aste, Naoki Yoshioka, Emiko Sakamoto, Noboru Saito
The bed nucleus of the stria terminalis pars medialis (BSTM), medial preoptic nucleus (POM), and lateral septal region (LS) exhibit more vasotocin-immunoreactive (VT-ir) neural structures in male than in female adult quail. VT-ir cells and fibers in these regions are sensitive to gonadal steroids only in males. The insensitivity of adult female VT-ir neural structures to sex steroids is attributed to estradiol exposure during a critical period in embryonic life. Although the VT-ir system has been intensively examined in adult quail, information is limited in embryos and juveniles...
May 5, 2016: Journal of Chemical Neuroanatomy
Xiaoqing Jia, Guangyu Liu, Jingyi Cheng, Zhenzhou Shen, Zhimin Shao
Studies have demonstrated that cysteine-rich 61 (CYR61) may be involved in tumor proliferation and invasion. However, little is known about the role of CYR61 plays in endocrine therapy. Here, we tested the CYR61 expression on human tissues from 36 primary breast cancer patients by immunohistochemistry staining before and after administrating letrozole , an oral non-steroidal aromatase inhibitor (AI) for the treatment of hormone-responsive breast cancer. The expression levels of CYR61 and ki67 were analyzed between pre-treatment and post-treatment samples by using the paired t test...
April 26, 2016: Current Cancer Drug Targets
Lucie Rárová, Jana Steigerová, Miroslav Kvasnica, Petr Bartůněk, Kateřina Křížová, Hana Chodounská, Zdeněk Kolář, David Sedlák, Jana Oklestkova, Miroslav Strnad
Structure-activity relationship analysis and profiling of a library of AB-functionalized cholestane derivatives closely related to brassinosteroids (BRs) were performed to examine their antiproliferative activities and activities on steroid hormone receptors. Some of the compounds were found to have strong cytotoxic activity in several human normal and cancer cell lines. The presence of a 3-hydroxy or 3-oxo group and 2,3-vicinal diol or 3,4-vicinal diol moiety were found to be necessary for optimum biological activity, as well as a six-membered B ring...
May 2016: Journal of Steroid Biochemistry and Molecular Biology
Ilhan Akan, Dona C Love, Katryn R Harwood, Michelle R Bond, John A Hanover
Gene expression during Drosophila development is subject to regulation by the Polycomb (Pc), Trithorax (Trx), and Compass chromatin modifier complexes. O-GlcNAc transferase (OGT/SXC) is essential for Pc repression suggesting that the O-GlcNAcylation of proteins plays a key role in regulating development. OGT transfers O-GlcNAc onto serine and threonine residues in intrinsically disordered domains of key transcriptional regulators; O-GlcNAcase (OGA) removes the modification. To pinpoint genomic regions that are regulated by O-GlcNAc levels, we performed ChIP-chip and microarray analysis after OGT or OGA RNAi knockdown in S2 cells...
May 6, 2016: Journal of Biological Chemistry
Timothy S C Hinks, Tom Brown, Laurie C K Lau, Hitasha Rupani, Clair Barber, Scott Elliott, Jon A Ward, Junya Ono, Shoichiro Ohta, Kenji Izuhara, Ratko Djukanović, Ramesh J Kurukulaaratchy, Anoop Chauhan, Peter H Howarth
BACKGROUND: Disease heterogeneity in patients with severe asthma and its relationship to inflammatory mechanisms remain poorly understood. OBJECTIVE: We aimed to identify and replicate clinicopathologic endotypes based on analysis of blood and sputum parameters in asthmatic patients. METHODS: One hundred ninety-four asthmatic patients and 21 control subjects recruited from 2 separate centers underwent detailed clinical assessment, sputum induction, and phlebotomy...
July 2016: Journal of Allergy and Clinical Immunology
Kirsty E Russell, Kian Fan Chung, Colin J Clarke, Andrew L Durham, Patrick Mallia, Joseph Footitt, Sebastian L Johnston, Peter J Barnes, Simon R Hall, Karen D Simpson, Malcolm R Starkey, Philip M Hansbro, Ian M Adcock, Coen H Wiegman
INTRODUCTION: Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine associated with acute and chronic inflammatory disorders and corticosteroid insensitivity. Its expression in the airways of patients with chronic obstructive pulmonary disease (COPD), a relatively steroid insensitive inflammatory disease is unclear, however. METHODS: Sputum, bronchoalveolar lavage (BAL) macrophages and serum were obtained from non-smokers, smokers and COPD patients...
2016: PloS One
L Zuccaro, A Cox, C Pray, K Radford, K Novakowski, M Dorrington, M G Surette, D Bowdish, P Nair
An increase in P13 Kinase activity and an associated reduction in histone deacetylase activity may contribute to both relative steroid insensitivity in patients with severe eosinophilic asthma and impaired macrophage scavenger function and susceptibility to recurrent infective bronchitis that may, in turn, contribute to further steroid insensitivity.
April 2016: Allergy
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