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Steroid insensitivity

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https://www.readbyqxmd.com/read/29233147/neutrophil-extracellular-traps-are-downregulated-by-glucocorticosteroids-in-lungs-in-an-equine-model-of-asthma
#1
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
#2
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...
December 6, 2017: 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
#3
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...
October 16, 2017: 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
#4
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...
October 18, 2017: 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
#5
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
#6
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/multi-tissue-transcriptomics-delineates-the-diversity-of-airway-t-cell-functions-in-asthma
#7
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 Sc 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 bronchoalveolar lavage were obtained from healthy subjects (N=19) and asthmatic patients (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...
September 21, 2017: 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
#8
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
#9
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
https://www.readbyqxmd.com/read/28720789/evolutionarily-conserved-bil4-suppresses-the-degradation-of-brassinosteroid-receptor-bri1-and-regulates-cell-elongation
#10
Ayumi Yamagami, Chieko Saito, Miki Nakazawa, Shozo Fujioka, Tomohiro Uemura, Minami Matsui, Masaaki Sakuta, Kazuo Shinozaki, Hiroyuki Osada, Akihiko Nakano, Tadao Asami, Takeshi Nakano
Brassinosteroids (BRs), plant steroid hormones, play important roles in plant cell elongation and differentiation. To investigate the mechanisms of BR signaling, we previously used the BR biosynthesis inhibitor Brz as a chemical biology tool and identified the Brz-insensitive-long hypocotyl4 mutant (bil4). Although the BIL4 gene encodes a seven-transmembrane-domain protein that is evolutionarily conserved in plants and animals, the molecular function of BIL4 in BR signaling has not been elucidated. Here, we demonstrate that BIL4 is expressed in early elongating cells and regulates cell elongation in Arabidopsis...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715798/bone-mineral-density-in-women-living-with-complete-androgen-insensitivity-syndrome-and-intact-testes-or-removed-gonads
#11
Silvano Bertelloni, Maria C Meriggiola, Elenora Dati, Antonio Balsamo, Giampiero I Baroncelli
Complete androgen insensitivity syndrome (CAIS) is due to complete androgen resistance in androgen-dependent tissues. Since androgens are involved in growth, development, and mass maintenance of the skeleton, bone health may be a relevant clinical issue for improving quality of life of women living with CAIS. Bone mineral density (BMD) in women with CAIS and intact gonads has been reported in a normal range, although exceptions are known showing a low BMD mainly at the lumbar level. In women with CAIS and removed gonads, BMD is usually reduced at both the lumbar spine and femoral neck...
2017: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
https://www.readbyqxmd.com/read/28645352/r%C3%A3-sistances-aux-hormones-st%C3%A3-ro%C3%A3-des-physiologie-et-pathologie-pathophysiology-of-steroid-resistance-syndrome
#12
N Ramos, M Lombès
Steroid resistance syndrome (mineralocorticoids, glucocorticoids, estrogens, androgens) is a rare clinical disorder, androgen insensitivity syndrome being the most commonly described. Resistance syndromes are characterized by elevated steroid hormone levels, secondary to an impaired signal transduction and a lack of negative feedback, without any specific clinical signs of steroid excess. In most cases, steroid hormone resistance is generally caused by steroid receptor mutations. Several nonsense and missense mutations or deletions have already been described for all steroid receptors, except for the progesterone receptor...
October 2016: Annales D'endocrinologie
https://www.readbyqxmd.com/read/28613048/is-the-second-to-fourth-digit-ratio-2d-4d-a-biomarker-of-sex-steroids-activity
#13
Vincenzo de Sanctis, Ashraf T Soliman, Heba Elsedfy, Nada Soliman, Rania Elalaily, Salvatore Di Maio
The second-to-fourth digit ratio (2D:4D) has been used as an indirect method to investigate the putative effects of prenatal exposure to androgens, and has been reported to be smaller in males than in females. This gender difference in digit length ratios has been linked with the in utero balance of androgens to oestrogen. This sexual dimorphism in 2D:4D ratios is apparent by 2 years of age and seems to be established early in life, possibly by the 14th week of gestation. Digits in females attain their maximum length at about 2...
June 2017: Pediatric Endocrinology Reviews: PER
https://www.readbyqxmd.com/read/28601781/cysteine-residues-244-and-458-459-within-the-catalytic-subunit-of-na-k-atpase-control-the-enzyme-s-hydrolytic-and-signaling-function-under-hypoxic-conditions
#14
Irina Yu Petrushanko, Vladimir A Mitkevich, Valentina A Lakunina, Anastasia A Anashkina, Pavel V Spirin, Peter M Rubtsov, Vladimir S Prassolov, Nikolay B Bogdanov, Pascal Hänggi, William Fuller, Alexander A Makarov, Anna Bogdanova
Our previous findings suggested that reversible thiol modifications of cysteine residues within the actuator (AD) and nucleotide binding domain (NBD) of the Na,K-ATPase may represent a powerful regulatory mechanism conveying redox- and oxygen-sensitivity of this multifunctional enzyme. S-glutathionylation of Cys244 in the AD and Cys 454-458-459 in the NBD inhibited the enzyme and protected cysteines' thiol groups from irreversible oxidation under hypoxic conditions. In this study mutagenesis approach was used to assess the role these cysteines play in regulation of the Na,K-ATPase hydrolytic and signaling functions...
May 31, 2017: Redox Biology
https://www.readbyqxmd.com/read/28576975/route-of-administration-affects-corticosteroid-sensitivity-of-a-combined-ovalbumin-and-lipopolysaccharide-model-of-asthma-exacerbation-in-guinea-pigs
#15
Alexander P P Lowe, Rhian S Thomas, Anthony T Nials, Emma J Kidd, Kenneth J Broadley, William R Ford
Lipopolysaccharide (LPS) contributes to asthma exacerbations and development of inhaled corticosteroid insensitivity. Complete resistance to systemic corticosteroids is rare, and most patients lie on a continuum of steroid responsiveness. This study aimed to examine the sensitivity of combined ovalbumin- (Ova) and LPS-induced functional and inflammatory responses to inhaled and systemic corticosteroid in conscious guinea pigs to test the hypothesis that the route of administration affects sensitivity. Guinea pigs were sensitized to Ova and challenged with inhaled Ova alone or combined with LPS...
August 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28554842/jasmonate-induced-biosynthesis-of-steroidal-glycoalkaloids-depends-on-coi1-proteins-in-tomato
#16
Ayman Abdelkareem, Chonprakun Thagun, Masaru Nakayasu, Masaharu Mizutani, Takashi Hashimoto, Tsubasa Shoji
In tomato, perception of jasmonates by a receptor complex, which includes the F-box protein CORONATINE INSENSITIVE 1 (COI1), elicits biosynthesis of defensive steroidal glycoalkaloids (SGAs) via a jasmonate-responsive ERF transcription factor, JRE4/GAME9. Although JRE4 is upregulated by jasmonate and induces the expression of many metabolic genes involved in SGA biosynthesis, it is not known whether JRE4 alone is sufficient for increased SGA biosynthesis upon activation of jasmonate signaling. Here, we show that application of methyl jasmonate induces the expression of JRE4 and SGA biosynthesis genes in leaves and hairy roots of wild-type tomato, but not in jasmonic acid insensitive 1 (jai1), a loss-of-function mutant allele of the tomato COI1 gene...
July 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28487303/female-phenotype-with-male-karyotype-a-clinical-enigma
#17
Suja Sukumar, Pavan Uppula, Santosh Kumar, Anil Bhansali
Development of gonadal and phenotypic sex during embryogenesis invariably corresponds to the genotypic sex. However, some disorders of sex development are associated with discordance between the chromosomal, gonadal or phenotypic sex which include complete androgen insensitivity syndrome, 46XY complete gonadal dysgenesis (Swyer syndrome) and, rarely, congenital adrenal hyperplasia due to CYP 17A1 (17α-hydroxylase) deficiency. The enzyme CYP17A1 includes 17α-hydroxylase and 17,20-lyase which are required for the synthesis of cortisol and sex steroids, respectively...
May 9, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28432720/androgen-receptor-dysfunction-as-a-prevalent-manifestation-in-young-male-carriers-of-a-flna-gene-mutation
#18
Laura Carrera-García, Maximiliano Francisco Rivas-Crespo, María Soledad Fernández García
Androgenic actions require the proper signal transmission by the androgen receptor (AR), a nuclear transcription factor. This is initially located in the cell cytoplasm and should translocates to the nucleus to interact with DNA. AR functional impairment causes diverse blockage degrees of androgenic steroid action, known as androgen insensitivity syndromes. Filamin A, a protein coded by the FLNA gene, is a co-activator of various cytoplasmic factors, including AR. The mutational inactivation of the FLNA gene induces insufficiency of translocation and activation of AR...
June 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28347742/corticosteroid-responses-of-snakes-to-toxins-from-toads-bufadienolides-and-plants-cardenolides-reflect-differences-in-dietary-specializations
#19
Shabnam Mohammadi, Susannah S French, Lorin A Neuman-Lee, Susan L Durham, Yosuke Kojima, Akira Mori, Edmund D Brodie, Alan H Savitzky
Toads are chemically defended by cardiotonic steroids known as bufadienolides. Resistance to the acute effects of bufadienolides in snakes that prey on toads is conferred by target-site insensitivity of the toxin's target enzyme, the Na(+)/K(+)-ATPase. Previous studies have focused largely on the molecular mechanisms of resistance but have not investigated the physiological mechanisms or consequences of exposure to the toxins. Adrenal enlargement in snakes often is associated with specialization on a diet of toads...
June 1, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28207417/adrenarche-unmasks-compound-heterozygous-3%C3%AE-hydroxysteroid-dehydrogenase-deficiency-c-244g-a-p-ala82thr-and-the-novel-931c-t-p-gln311-variant-in-a-non-salt-wasting-severely-undervirilised-46xy
#20
Stephanie Louise Teasdale, Adam Morton
3β-Hydroxysteroid dehydrogenase type II deficiency (3βHSD2) congenital adrenal hyperplasia is a rare cause of ambiguous genitalia, resulting in abnormal virilisation in both 46XY and 46XX. We describe a case of 46XY ambiguous genitalia that was misdiagnosed as androgen insensitivity syndrome. The correct diagnosis was made after adrenarche. Genotyping demonstrated compound heterozygosity in two alleles, the previously described c.244G>A (p.Ala82Thr), and a novel 931C>T(p.Gln311*) variant. We suggest that adrenarche unmasked the condition by driving cortisol production to rates that caused the mutant 3bHSD2 enzyme to become rate limiting for cortisol production...
March 1, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
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