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https://www.readbyqxmd.com/read/28550712/combined-immune-checkpoint-blockade-anti-pd-1-anti-ctla-4-evaluation-and-management-of-adverse-drug-reactions
#1
REVIEW
Jessica C Hassel, Lucie Heinzerling, Jens Aberle, Oliver Bähr, Thomas K Eigentler, Marc-Oliver Grimm, Victor Grünwald, Jan Leipe, Niels Reinmuth, Julia K Tietze, Jörg Trojan, Lisa Zimmer, Ralf Gutzmer
Combined immune checkpoint blockade (ICB) provides unprecedented efficacy gains in numerous cancer indications, with PD-1 inhibitor nivolumab plus CTLA-4 inhibitor ipilimumab in advanced melanoma as first-ever approved therapies for combined ICB. However, gains in efficacy must be balanced against a higher frequency and severity of adverse drug reactions (ADR). Because delays in diagnosis and management might result in symptom worsening and further complications, clinicians shall be well trained to identify ADR promptly and monitor patients adequately...
May 18, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28550404/development-of-an-imaging-system-for-in-vivo-real-time-monitoring-of-neuronal-activity-in-deep-brain-of-free-moving-rats
#2
Norio Iijima, Shinji Miyamoto, Keisuke Matsumoto, Ken Takumi, Yoichi Ueta, Hitoshi Ozawa
We have newly developed a system that allows monitoring of the intensity of fluorescent signals from deep brains of rats transgenically modified to express enhanced green fluorescent protein (eGFP) via an optical fiber. One terminal of the optical fiber was connected to a blue semiconductor laser oscillator/green fluorescence detector. The other terminal was inserted into the vicinity of the eGFP-expressing neurons. Since the optical fiber was vulnerable to twisting stresses caused by animal movement, we also developed a cage in which the floor automatically turns, in response to the turning of the rat's head...
May 26, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28550372/tnf%C3%AE-induced-dlk-activation-contributes-to-apoptosis-in-the-beta-cell-line-hit
#3
Svenja Börchers, Rohollah Babaei, Catarina Klimpel, Jorge Duque Escobar, Sabine Schröder, Roland Blume, Muhammad Nasir Hayat Malik, Elke Oetjen
Reduction in beta-cell mass and function contributes to the pathogenesis of diabetes mellitus type 2. The proinflammatory cytokines tumor necrosis factor (TNF)α and interleukin (IL)-1β have been implicated in the pathogenesis of this disease. Overexpression of the dual leucine zipper kinase (DLK) inhibits beta-cell function and induces apoptosis in the beta-cell line HIT. In the present study, it was investigated whether TNFα or IL-1β stimulates DLK enzymatic activity. Immunoblot analysis, transient transfection with luciferase reporter gene assays, and immunofluorescence were used...
May 27, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28550272/non-alcoholic-fatty-liver-disease-a-chronic-disease-of-the-21-st-century
#4
Metrakos Peter, Nilsson Tommy
Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of metabolic states ranging from simple steatosis to inflammation with associated fibrosis to cirrhosis. Though accumulation of hepatic fat is not associated with a significant increase in mortality rates, hepatic inflammation is, as this augments the risk of terminal liver disease, i.e., cirrhosis, hepatic decompensation (liver failure) and/or hepatocellular carcinoma. Disease progression is usually slow, over a decade or more and, for the most part, remains asymptomatic...
May 26, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28550201/the-influence-of-mhc-class-ii-on-b-cell-defects-induced-by-invariant-chain-cd74-n-terminal-fragments
#5
Janna Schneppenheim, Ann-Christine Loock, Susann Hüttl, Michaela Schweizer, Renate Lüllmann-Rauch, Hans-Heinrich Oberg, Philipp Arnold, Christian H K Lehmann, Diana Dudziak, Dieter Kabelitz, Ralph Lucius, Ana-Maria Lennon-Duménil, Paul Saftig, Bernd Schröder
The invariant chain (CD74) mediates assembly and targeting of MHC class II (MHCII) complexes. In endosomes, CD74 undergoes sequential degradation by different proteases, including cathepsin S (CatS) and the intramembrane protease signal peptide peptidase-like 2a (SPPL2a). In their absence, CD74 N-terminal fragments (NTFs) accumulate. In SPPL2a(-/-) B cells, such an NTF impairs endosomal trafficking and BCR signal transduction. In mice, this leads to a loss of splenic B cells beyond the transitional stage 1...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550199/comprehensive-approach-for-identifying-the-t-cell-subset-origin-of-cd3-and-cd28-antibody-activated-chimeric-antigen-receptor-modified-t-cells
#6
Michael Schmueck-Henneresse, Bilal Omer, Thomas Shum, Haruko Tashiro, Maksim Mamonkin, Natalia Lapteva, Sandhya Sharma, Lisa Rollins, Gianpietro Dotti, Petra Reinke, Hans-Dieter Volk, Cliona M Rooney
The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45RO(+)CCR7(-) effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28-activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550138/altered-regulation-of-erk1b-by-mek1-and-ptp-sl-and-modified-elk1-phosphorylation-by-erk1b-are-caused-by-abrogation-of-the-regulatory-c-terminal-sequence-of-erks
#7
Yuval Yung, Zhong Yao, Daniel M Aebersold, Tamar Hanoch, Rony Seger
No abstract text is available yet for this article.
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28550134/gq-protein-induced-apoptosis-is-mediated-by-akt-kinase-inhibition-that-leads-to-protein-kinase-c-induced-c-jun-n-terminal-kinase-activation
#8
Ido Ben-Ami, Zhong Yao, Zvi Naor, Rony Seger
No abstract text is available yet for this article.
May 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28550115/involvement-of-cell-surface-90-kda-heat-shock-protein-hsp90-in-pattern-recognition-by-human-monocyte-derived-macrophages
#9
Małgorzata Bzowska, Anna Nogieć, Krystian Bania, Magdalena Zygmunt, Mirosław Zarębski, Jerzy Dobrucki, Krzysztof Guzik
Heat shock proteins (HSPs) are typical intracellular chaperones which also appear on the cell surface and in extracellular milieu. HSP90, which chaperones many proteins involved in signal transduction, is also a regular component of LPS-signaling complexes on Mϕ. As LPS is a prototypical PAMP, we speculated that HSP90 is engaged in pattern recognition by professional phagocytes. In this report, we provide the first evidence, to our knowledge, of the geldanamycin (Ge)-inhibitable HSP90 on the surface of live monocyte-derived Mϕs (hMDMs)...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550100/an-alternative-surgical-approach-reduces-variability-following-filament-induction-of-experimental-stroke-in-mice
#10
M Trotman-Lucas, M E Kelly, J Janus, R Fern, C L Gibson
Animal models are critical for understanding the pathology of stroke and investigating potential treatments. However, in vivo stroke models are associated, particularly in mice, with high variability in lesion volume. We investigated whether a surgical refinement where reperfusion is not reliant on the Circle of Willis reduced outcome variability. Mice underwent 60 minutes of transient middle cerebral artery occlusion avoiding ligation of the external carotid artery. During reperfusion the common carotid artery was either ligated (standard approach), or it was repaired to allow re-establishment of blood flow through the common carotid artery...
May 26, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28549954/amlexanox-enhances-premature-termination-codon-read-through-in-col7a1-and-expression-of-full-length-type-vii-collagen-potential-therapy-for-recessive-dystrophic-epidermolysis-bullosa
#11
Velina S Atanasova, Qiujie Jiang, Marco Prisco, Christina Gruber, Josefina Piñón Hofbauer, Mei Chen, Cristina Has, Leena Bruckner-Tuderman, John A McGrath, Jouni Uitto, Andrew P South
Recessive dystrophic epidermolysis bullosa (RDEB) is a rare monogenic blistering disorder caused by lack of functional type VII collagen, leading to skin fragility and subsequent trauma-induced separation of the epidermis from the underlying dermis. 46% of RDEB patients harbor at least one premature termination codon (PTC) mutation in COL7A1 and previous studies have shown that aminoglycosides are able to overcome RDEB PTC mutations by inducing "read-through" and incorporation of an amino acid at the PTC site...
May 23, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28549941/dietary-zinc-deficiency-reduced-growth-performance-intestinal-immune-and-physical-barrier-functions-related-to-nf-%C3%AE%C2%BAb-tor-nrf2-jnk-and-mlck-signaling-pathway-of-young-grass-carp-ctenopharyngodon-idella
#12
Zheng-Xing Song, Wei-Dan Jiang, Yang Liu, Pei Wu, Jun Jiang, Xiao-Qiu Zhou, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Lin Feng
Our study investigated the effects of dietary zinc (Zn) deficiency on growth performance, intestinal immune and physical barrier functions of young grass carp (Ctenopharyngodon idella). A total of 630 grass carp (244.14 ± 0.40 g) were fed graded levels of zinc lactate (10.71, 30.21, 49.84, 72.31, 92.56, 110.78 mg Zn/kg diet) and one zinc sulfate group (56.9 mg Zn/kg diet) for 60 days. At the end of the feeding trial, fish were challenged with Aeromonas hydrophila for 14 days. These results indicated that compared with optimal dietary Zn level, dietary Zn deficiency (10...
May 23, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28549935/the-conserved-domain-in-morf-proteins-has-distinct-affinities-to-the-ppr-and-e-elements-in-ppr-rna-editing-factors
#13
Eszter Bayer-Császár, Sascha Haag, Anja Jörg, Franziska Glass, Barbara Härtel, Toshihiro Obata, Etienne H Meyer, Axel Brennicke, Mizuki Takenaka
In plant organelles specific nucleotide motifs at C to U RNA editing sites are recognized by the PLS-class of pentatricopeptide repeat (PPR) proteins, which are additionally characterized by a C-terminal E domain. The PPR elements bind the nucleotides in the target RNA, while the function of the E domain has remained unknown. At most sites RNA editing also requires multiple organellar RNA editing factor (MORF) proteins. To understand how these two types of proteins are involved in RNA editing complexes, we systematically analyzed their protein-protein interactions...
May 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28549905/on-the-use-of-group-sequential-study-designs-for-the-test-of-bioequivalence-for-complicated-products
#14
Rajesh Krishna, Wen-Lin Luo, Patrick J Larson, Paul H Fackler
A novel modeling approach together with a use of group sequential study design for a complicated triple fixed-dose combination was attempted. Probability of success (POS) was used for determining a weighted average power, where weight was based on available information such as data from previous pilot studies or literature. A simulation study was conducted that resulted in the development of the necessary sample size for the studies in addition to identifying a decision algorithm that was prospectively defined in the protocols...
May 23, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28549860/crude-terpene-glycoside-component-from-radix-paeoniae-rubra-protects-against-isoproterenol-induced-myocardial-ischemic-injury-via-activation-of-the-pi3k-akt-mtor-signaling-pathway
#15
Zhongcheng Ke, Gang Wang, Lei Yang, Huihui Qiu, Hao Wu, Mei Du, Juan Chen, Jie Song, Xiaobin Jia, Liang Feng
ETHNOPHARMACOLOGICAL RELEVANCE: Radix paeoniae rubra, also known as chishao (CS), is a frequently used traditional Chinese medicine that can promote blood circulation to remove blood stasis. It has been widely used for the prevention and treatment of cardiovascular diseases in China. Although terpene glycoside (TG), the major component in CS, has been shown to possess cardioprotective properties, the mechanism underlying CS-TG's preventive effect against myocardial ischemia injury is unknown...
May 23, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28549769/variations-in-the-cerebrospinal-fluid-proteome-following-traumatic-brain-injury-and-subarachnoid-hemorrhage
#16
David E Connor, Ganta V Chaitanya, Prashant Chittiboina, Paul McCarthy, L Keith Scott, Lisa Schrott, Alireza Minagar, Anil Nanda, J Steven Alexander
BACKGROUND: Proteomic analysis of cerebrospinal fluid (CSF) has shown great promise in identifying potential markers of injury in neurodegenerative diseases [1-13]. Here we compared CSF proteomes in healthy individuals, with patients diagnosed with traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) in order to characterize molecular biomarkers which might identify these different clinical states and describe different molecular mechanisms active in each disease state. METHODS: Patients presenting to the Neurosurgery service at the Louisiana State University Hospital-Shreveport with an admitting diagnosis of TBI or SAH were prospectively enrolled...
May 13, 2017: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/28549735/optimization-of-the-process-of-inverted-peptides-pipe-plus-to-screen-pdz-domain-ligands
#17
Quentin Seisel, Marisa Rädisch, Nicholas P Gill, Dean R Madden, Prisca Boisguerin
PDZ domains play crucial roles in cell signaling processes and are therefore attractive targets for the development of therapeutic inhibitors. In many cases, C-terminal peptides are the physiological binding partners of PDZ domains. To identify both native ligands and potential inhibitors we have screened arrays synthesized by the process of inverted peptides (PIPE), a variant of SPOT synthesis that generates peptides with free C-termini. Here, we present the development of a new functionalized cellulose membrane as solid support along with the optimized PIPE(PLUS) technology...
May 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28549670/cilastatin-attenuates-vancomycin-induced-nephrotoxicity-via-p-glycoprotein
#18
Dai Sig Im, Hye Jin Shin, Keum Jin Yang, So Young Jung, Ho Yeon Song, Hyeon Seok Hwang, Hyo-Wook Gil
BACKGROUND: Oxidative stress is one of the main pathogenic mechanisms in vancomycin-induced nephrotoxicity (VIN). Some studies suggest proximal renal tubular cell necrosis by vancomycin accumulation as a mechanism of nephrotoxicity, and other studies demonstrate that cilastatin has protective effects against drug-induced nephrotoxicity. We investigated whether cilastatin regulates P-gp expression and whether cilastation prevents VIN. MATERIALS AND METHODS: We conducted an in vitro study using an immortalized proximal tubule epithelial cell line from a normal adult human kidney (HK-2) and an in vivo study using male C57BL/6J mice...
May 23, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28549648/characterization-of-long-term-gait-deficits-in-mouse-dmcao-using-the-catwalk-system
#19
E Caballero-Garrido, J C Pena-Philippides, Z Galochkina, E Erhardt, T Roitbak
Evaluation of functional outcome is widely used across species to assess the recovery process following various pathological conditions, including spinal cord injury, musculo-skeletal injury, mithochondrial disease, neuropathic cancer, Huntington's disease, chronic pain, cortical lesion, and olivocerebellar degeneration among others. The Stroke Therapy Academic Industry Roundtable (STAIR) recommends multiple endpoints for behavioral studies in pre-clinical stroke research, to demonstrate their clinical relevance...
May 23, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28549491/increased-chondrocyte-apoptosis-in-kashin-beck-disease-and-rats-induced-by-t-2-toxin-and-selenium-deficiency
#20
Hao Jie Yang, Ying Zhang, Zhi Lun Wang, Sen Hai Xue, Si Yuan Li, Xiao Rong Zhou, Meng ZHANGg, Qian Fang, Wen Jun Wang, Chen Chen, Xiang Hua Deng, Jing Hong Chen
OBJECTIVE: To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease (KBD) and in an established T-2 toxin- and selenium (Se) deficiency-induced rat model. METHODS: Cartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase dUTP nick end labeling staining...
May 2017: Biomedical and Environmental Sciences: BES
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