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https://www.readbyqxmd.com/read/28538184/taxane-platin-resistant-lung-cancers-co-develop-hypersensitivity-to-jumonjic-demethylase-inhibitors
#1
Maithili P Dalvi, Lei Wang, Rui Zhong, Rahul K Kollipara, Hyunsil Park, Juan Bayo, Paul Yenerall, Yunyun Zhou, Brenda C Timmons, Jaime Rodriguez-Canales, Carmen Behrens, Barbara Mino, Pamela Villalobos, Edwin R Parra, Milind Suraokar, Apar Pataer, Stephen G Swisher, Neda Kalhor, Natarajan V Bhanu, Benjamin A Garcia, John V Heymach, Kevin Coombes, Yang Xie, Luc Girard, Adi F Gazdar, Ralf Kittler, Ignacio I Wistuba, John D Minna, Elisabeth D Martinez
Although non-small cell lung cancer (NSCLC) patients benefit from standard taxane-platin chemotherapy, many relapse, developing drug resistance. We established preclinical taxane-platin-chemoresistance models and identified a 35-gene resistance signature, which was associated with poor recurrence-free survival in neoadjuvant-treated NSCLC patients and included upregulation of the JumonjiC lysine demethylase KDM3B. In fact, multi-drug-resistant cells progressively increased the expression of many JumonjiC demethylases, had altered histone methylation, and, importantly, showed hypersensitivity to JumonjiC inhibitors in vitro and in vivo...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538172/using-hescs-to-probe-the-interaction-of-the-diabetes-associated-genes-cdkal1-and-mt1e
#2
Min Guo, Tuo Zhang, Xue Dong, Jenny Zhaoying Xiang, Minxiang Lei, Todd Evans, Johannes Graumann, Shuibing Chen
Genome-wide association studies (GWASs) have identified many disease-associated variant alleles, but understanding whether and how different genes/loci interact requires a platform for probing how the variant alleles act mechanistically. Isogenic mutant human embryonic stem cells (hESCs) provide an unlimited resource to derive and study human disease-relevant cells. Here, we focused on CDKAL1, linked by GWASs to diabetes. Through transcript profiling, we find that expression of the metallothionein (MT) gene family, also linked by GWASs to diabetes, is significantly downregulated in CDKAL1(-/-) cells that have been differentiated to insulin-expressing pancreatic beta-like cells...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28537933/hypersensitivity-reactions-to-gadolinium-based-contrast-agents
#3
Jie Shen Fok, William B Smith
PURPOSE OF REVIEW: Gadolinium-based contrast agents (GBCAs) have been utilized since the late 1980s to enhance the diagnostic value of MRI studies. They are known to have excellent safety profile and serious adverse reactions are uncommon despite widespread global use. However, immediate hypersensitivity reactions are well described in the literature, with urticaria the most common manifestation. Anaphylaxis can occur, though fatality is extremely rare. This review explores the incidence of GBCA-related hypersensitivity reactions and highlights potential risk factors...
May 22, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28537805/pathology-of-chronic-hypersensitivity-pneumonitis-what-is-it-what-are-the-diagnostic-criteria-why-do-we-care
#4
Andrew Churg, AnaMaria Bilawich, Joanne L Wright
CONTEXT: - Chronic hypersensitivity pneumonitis (CHP) has emerged from obscurity during the past 15 years and is now recognized as a very common form of fibrosing interstitial pneumonia but one that is frequently misdiagnosed both clinically and on surgical lung biopsy as usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) or fibrotic nonspecific interstitial pneumonia. OBJECTIVE: - To review the pathologic features of CHP. DATA SOURCES: - Clinical, pathology, and radiology literature were used...
May 24, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28535413/controllable-synthesis-and-luminescent-properties-of-rare-earth-doped-gd2-moo4-3-nanoplates
#5
Lei Zhang, Bohua Dong, Guohua Wang, Rongjie Gao, Ge Su, Wei Wang, Lixin Cao
For the first time, we have successfully synthesized rare-earth doped Gd2(MoO4)3: RE(3+) (RE=Eu, Tb) nanoplates by solvothermal method. The morphology of Gd2(MoO4)3 can be manipulated by changing the reaction times and reaction temperatures. The composition and surface morphology have been investigated by X-ray powder diffraction (XRD) and transmission electron microscopy (TEM), respectively. Under the excitation of UV, Photoluminescence (PL) has been used to explore the excellent luminescence properties of the synthesized nanophosphors...
April 21, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28535155/elevated-apobec3b-expression-drives-a-kataegic-like-mutation-signature-and-replication-stress-related-therapeutic-vulnerabilities-in-p53-defective-cells
#6
Jenni Nikkilä, Rahul Kumar, James Campbell, Inger Brandsma, Helen N Pemberton, Fredrik Wallberg, Kinga Nagy, Ildikó Scheer, Beata G Vertessy, Artur A Serebrenik, Valentina Monni, Reuben S Harris, Stephen J Pettitt, Alan Ashworth, Christopher J Lord
BACKGROUND: Elevated APOBEC3B expression in tumours correlates with a kataegic pattern of localised hypermutation. We assessed the cellular phenotypes associated with high-level APOBEC3B expression and the influence of p53 status on these phenotypes using an isogenic system. METHODS: We used RNA interference of p53 in cells with inducible APOBEC3B and assessed DNA damage response (DDR) biomarkers. The mutational effects of APOBEC3B were assessed using whole-genome sequencing...
May 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28533366/mechanism-of-h2s-mediated-protection-against-oxidative-stress-in-escherichia-coli
#7
Alexander Mironov, Tatyana Seregina, Maxim Nagornykh, Lyly G Luhachack, Natalya Korolkova, Liubov Errais Lopes, Vera Kotova, Gennady Zavilgelsky, Rustem Shakulov, Konstantin Shatalin, Evgeny Nudler
Endogenous hydrogen sulfide (H2S) renders bacteria highly resistant to oxidative stress, but its mechanism remains poorly understood. Here, we report that 3-mercaptopyruvate sulfurtransferase (3MST) is the major source of endogenous H2S in Escherichia coli Cellular resistance to H2O2 strongly depends on the activity of mstA, a gene that encodes 3MST. Deletion of the ferric uptake regulator (Fur) renders ∆mstA cells hypersensitive to H2O2 Conversely, induction of chromosomal mstA from a strong pLtetO-1 promoter (P tet -mstA) renders ∆fur cells fully resistant to H2O2 Furthermore, the endogenous level of H2S is reduced in ∆fur or ∆sodA ∆sodB cells but restored after the addition of an iron chelator dipyridyl...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533182/biased-visceral-perception-through-fear-learning-biased-intensity-judgements-of-visceral-sensations-after-learning-to-fear-visceral-stimuli-a-drift-diffusion-approach
#8
Jonas Zaman, Victoria J Madden, Julie Iven, Katja Wiech, Nathalie Weltens, Huynh Giao Ly, Johan W S Vlaeyen, Lukas Van Oudenhove, Ilse Van Diest
A growing body of research has identified fear of visceral sensations as a potential mechanism in the development and maintenance of visceral pain disorders. However, the extent to which such learned fear affects visceroception remains unclear. To address this question, we used a differential fear conditioning paradigm with non-painful esophageal balloon distensions of two different intensities as conditioning stimuli (CSs). The experiment comprised pre-acquisition, acquisition and post-acquisition phases during which participants categorized the CSs with respect to their intensity...
May 19, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28531655/competitive-adsorption-behavior-toward-metal-ions-on-nano-fe-mg-ni-ternary-layered-double-hydroxide-proved-by-xps-evidence-of-selective-and-sensitive-detection-of-pb-ii
#9
Shan-Shan Li, Min Jiang, Tian-Jia Jiang, Jin-Huai Liu, Zheng Guo, Xing-Jiu Huang
Hypersensitive and highly selective nanomaterials for the measurement of heavy metal ions (HMIs) hold a key to electro-analysis. Various works improved the results of analysis but without scientific understanding. Herein, Fe/Mg/Ni-layered double hydroxide (LDH) has been successfully prepared and its electrochemical behavior for Pb(II) detection is also studied using square wave anodic stripping voltammetry (SWASV). The well performance of electrochemistry suggest that the modification with Fe/Mg/Ni-LDH significantly promotes the selectivity and sensitivity toward Pb(II)...
May 11, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28530675/reevaluation-of-snp-heritability-in-complex-human-traits
#10
Doug Speed, Na Cai, Michael R Johnson, Sergey Nejentsev, David J Balding
SNP heritability, the proportion of phenotypic variance explained by SNPs, has been reported for many hundreds of traits. Its estimation requires strong prior assumptions about the distribution of heritability across the genome, but current assumptions have not been thoroughly tested. By analyzing imputed data for a large number of human traits, we empirically derive a model that more accurately describes how heritability varies with minor allele frequency (MAF), linkage disequilibrium (LD) and genotype certainty...
May 22, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28530662/pd-l1-inhibits-acute-and-chronic-pain-by-suppressing-nociceptive-neuron-activity-via-pd-1
#11
Gang Chen, Yong Ho Kim, Hui Li, Hao Luo, Da-Lu Liu, Zhi-Jun Zhang, Mark Lay, Wonseok Chang, Yu-Qiu Zhang, Ru-Rong Ji
Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through the receptor PD-1 expressed on T cells. However, the role of PD-L1 and PD-1 in regulating pain and neuronal function is unclear. Here we report that both melanoma and normal neural tissues including dorsal root ganglion (DRG) produce PD-L1 that can potently inhibit acute and chronic pain. Intraplantar injection of PD-L1 evoked analgesia in naive mice via PD-1, whereas PD-L1 neutralization or PD-1 blockade induced mechanical allodynia...
May 22, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28529998/complement-c5a-receptor-is-the-key-initiator-of-neutrophil-adhesion-igniting-immune-complex-induced-arthritis
#12
Yoshishige Miyabe, Chie Miyabe, Thomas T Murooka, Edward Y Kim, Gail A Newton, Nancy D Kim, Bodduluri Haribabu, Francis W Luscinskas, Thorsten R Mempel, Andrew D Luster
The deposition of immune complexes (IC) in tissues induces a "type III hypersensitivity" that results in tissue damage and underlies the pathogenesis of many autoimmune diseases. The neutrophil is the first immune cell recruited into sites of IC deposition and plays a critical role in shaping the overall tissue response. However, the mechanism by which IC initiate and propagate neutrophil infiltration into tissue is not known. Here, using intravital multiphoton joint imaging of IC-induced arthritis in live mice, we found that the complement C5a receptor (C5aR) was the key initiator of neutrophil adhesion on joint endothelium...
January 2017: Science Immunology
https://www.readbyqxmd.com/read/28529242/hyperuricemia-as-a-protective-factor-for-mild-cognitive-impairment-in-non-obese-elderly
#13
Feng Wang, Minghui Zhao, Zhaoli Han, Dai Li, Shishuang Zhang, Yongqiang Zhang, Xiaodong Kong, Ning Sun, Qiang Zhang, Ping Lei
Mild cognitive impairment (MCI) is regarded as incipient dementia. Patients with MCI have increased risk of later progressing to dementia. Blood uric acid (UA) is an important non-enzymatic antioxidant in peripheral circulation, and plays an unconfirmed protective role in MCI. Furthermore, obesity-induced inflammation, which affects UA metabolism and MCI onset, might regulate such protective role. Thus, the aim of the study was to determine the relationship of UA to MCI and the potential effect from inflammation...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28527770/metallic-coronary-stents-is-there-a-relationship-between-stent-fracture-and%C3%A2-hypersensitivity
#14
Hiroyoshi Mori, Robert Kutys, Maria Romero, Renu Virmani, Aloke V Finn
No abstract text is available yet for this article.
May 11, 2017: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28527278/-drug-rash-with-eosinophilia-and-systemic-symptoms-syndrome-induced-by-carbamazepine-case-report
#15
Jorge Alonso Marín, Mayra Alexandra Ortega, Isaura Pilar Sánchez, José Armando Pacheco
Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a hypersensitivity reaction associated with a variety of drugs, mainly anticonvulsants, which is characterized by systemic symptoms and erythematous lesions, common to other toxicodermas. It is an uncommon clinical entity that requires a high suspicion by clinical staff given its varied initial presentation, and the fact that symptoms can overlap with those of other adverse cutaneous reactions to drugs. Without early diagnosis and appropriate treatment, mortality increases...
June 1, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28526335/the-spider-toxin-ph%C3%AE-1%C3%AE-recombinant-possesses-strong-analgesic-activity
#16
Flavia Karine Rigo, Gabriela Trevisan, Samira Dal-Toé De Prá, Marta Nascimento Cordeiro, Marcia Helena Borges, Juliana Figueiredo Silva, Flavia Viana Santa Cecilia, Alessandra Hubner de Souza, Gabriela de Oliveira Adamante, Alessandra Marcon Milioli, Célio José de Castro Junior, Juliano Ferreira, Marcus Vinicius Gomez
The native Phα1β - a Voltage-Gated Calcium Channel (VGCC) blocker - and its Recombinant Version - were both tested in rodent pain models with an intraplantar injections of capsaicin or formalin, a chronic constriction injury, and melanoma cancer related pain. The formalin nociceptive behaviour in the neurogenic phase was not affected by the toxin pre-treatments, while in the inflammatory phase, Phα1β and the Recombinant form caused a significant reduction. The nociception that was triggered by capsaicin, an agonist of the TRPV1 vanilloid receptor, was totally blocked by 100 pmol/site, i...
May 17, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28526294/central-amygdala-activation-of-extracellular-signal-regulated-kinase-1-and-age-dependent-changes-in-inflammatory-pain-sensitivity-in-mice
#17
Katelyn E Sadler, Nathan M Gartland, Jane E Cavanaugh, Benedict J Kolber
Aging populations are more sensitive to noxious stimuli as a result of altered somatosensory systems. In these experiments, we examined pain-like behaviors in young, middle-aged, and old mice during peripheral inflammation to determine if the same sensitivity exists in preclinical animal models. Immediately following injury, middle-aged and old mice exhibited more spontaneous pain-like behaviors than young mice, matching pain prevalence in clinical populations. Middle-aged and old mice also developed persistent mechanical hypersensitivity in the injured paw...
April 26, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28526275/increasing-total-serum-ige-allergic-bronchopulmonary-aspergillosis-and-lung-function-in-cystic-fibrosis
#18
Florian Gothe, Matthias Kappler, Matthias Griese
BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disorder contributing to lung disease in cystic fibrosis (CF) and challenging to diagnose. OBJECTIVE: This study analyzed the predictive value of increasing total IgE (t-IgE) levels in a CF cohort alongside with clinical and serologic data. METHODS: A total of 387 children and young adults were followed from 2000 to 2006 and retrospectively classified into 6 groups...
May 16, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28525717/synthesis-and-biological-evaluation-of-novel-neuroprotective-pyridazine-derivatives-as-excitatory-amino-acid-transporter-2-eaat2-activators
#19
Alessia Chelini, Simone Brogi, Marco Paolino, Angela Di Capua, Andrea Cappelli, Gianluca Giorgi, Mersedeh Farzad, Lorenzo Di Cesare Mannelli, Laura Micheli, Carla Ghelardini, Maurizio Anzini
LDN-212320 (3) was found to be a potent EAAT2 activator at a translational level, restoring the normal clearance of glutamate and providing neuronal protection. Since the pharmacologic activation of EAAT2 represents a valuable strategy to relieve neuropathic pain, we synthesized novel activators (4a-f) of EAAT2. Among them 4f, analysed in comparison with compound 3 in different rat models of oxaliplatin-induced neuropathic pain, showed the better anti-hypersensitive profile being able to fully counteract the oxaliplatin-induced neuropathy...
May 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28525664/near-infrared-fluorescence-with-indocyanine-green-for-diagnostics-in-urology-initial-experience
#20
Andrey O Morozov, Yuri G Alyaev, Leonid M Rapoport, Dmitrii G Tsarichenko, Eugene A Bezrukov, Denis V Butnaru, Eugene S Sirota
INTRODUCTION: Fluorescence imaging with indocyanine green is used in urology for the detection of sentinel lymph nodes and identification of prostate margins in radical prostatectomy for delineation of resection zone and selective clamping of vessels in partial nephrectomy; for identification and evaluation of length of ureteral strictures; for assessment of perfusion and viability of anastomoses during reconstructive stage of cystectomy. Safety of this technique is proven, while its diagnostic value and usefulness is still controversial...
May 16, 2017: Urologia
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