journal
MENU ▼
Read by QxMD icon Read
search

Journal of Clinical Investigation

journal
https://www.readbyqxmd.com/read/27893465/accelerated-resolution-of-inflammation-underlies-sex-differences-in-inflammatory-responses-in-humans
#1
Krishnaraj S Rathod, Vikas Kapil, Shanti Velmurugan, Rayomand S Khambata, Umme Siddique, Saima Khan, Sven Van Eijl, Lorna C Gee, Jascharanpreet Bansal, Kavi Pitrola, Christopher Shaw, Fulvio D'Acquisto, Romain A Colas, Federica Marelli-Berg, Jesmond Dalli, Amrita Ahluwalia
BACKGROUND: Cardiovascular disease occurs at lower incidence in premenopausal females compared with age-matched males. This variation may be linked to sex differences in inflammation. We prospectively investigated whether inflammation and components of the inflammatory response are altered in females compared with males. METHODS: We performed 2 clinical studies in healthy volunteers. In 12 men and 12 women, we assessed systemic inflammatory markers and vascular function using brachial artery flow-mediated dilation (FMD)...
November 28, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27893464/the-h3k9-dimethyltransferases-ehmt1-2-protect-against-pathological-cardiac-hypertrophy
#2
Bernard Thienpont, Jan Magnus Aronsen, Emma Louise Robinson, Hanneke Okkenhaug, Elena Loche, Arianna Ferrini, Patrick Brien, Kanar Alkass, Antonio Tomasso, Asmita Agrawal, Olaf Bergmann, Ivar Sjaastad, Wolf Reik, Hywel Llewelyn Roderick
Cardiac hypertrophic growth in response to pathological cues is associated with reexpression of fetal genes and decreased cardiac function and is often a precursor to heart failure. In contrast, physiologically induced hypertrophy is adaptive, resulting in improved cardiac function. The processes that selectively induce these hypertrophic states are poorly understood. Here, we have profiled 2 repressive epigenetic marks, H3K9me2 and H3K27me3, which are involved in stable cellular differentiation, specifically in cardiomyocytes from physiologically and pathologically hypertrophied rat hearts, and correlated these marks with their associated transcriptomes...
November 28, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27893463/inhibition-of-the-gas6-axl-pathway-augments-the-efficacy-of-chemotherapies
#3
Mihalis S Kariolis, Yu Rebecca Miao, Anh Diep, Shannon E Nash, Monica M Olcina, Dadi Jiang, Douglas S Jones, Shiven Kapur, Irimpan I Mathews, Albert C Koong, Erinn B Rankin, Jennifer R Cochran, Amato J Giaccia
The AXL receptor and its activating ligand, growth arrest-specific 6 (GAS6), are important drivers of metastasis and therapeutic resistance in human cancers. Given the critical roles that GAS6 and AXL play in refractory disease, this signaling axis represents an attractive target for therapeutic intervention. However, the strong picomolar binding affinity between GAS6 and AXL and the promiscuity of small molecule inhibitors represent important challenges faced by current anti-AXL therapeutics. Here, we have addressed these obstacles by engineering a second-generation, high-affinity AXL decoy receptor with an apparent affinity of 93 femtomolar to GAS6...
November 28, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27893462/biallelic-mutations-in-irf8-impair-human-nk-cell-maturation-and-function
#4
Emily M Mace, Venetia Bigley, Justin T Gunesch, Ivan K Chinn, Laura S Angelo, Matthew A Care, Sheetal Maisuria, Michael D Keller, Sumihito Togi, Levi B Watkin, David F LaRosa, Shalini N Jhangiani, Donna M Muzny, Asbjørg Stray-Pedersen, Zeynep Coban Akdemir, Jansen B Smith, Mayra Hernández-Sanabria, Duy T Le, Graham D Hogg, Tram N Cao, Aharon G Freud, Eva P Szymanski, Sinisa Savic, Matthew Collin, Andrew J Cant, Richard A Gibbs, Steven M Holland, Michael A Caligiuri, Keiko Ozato, Silke Paust, Gina M Doody, James R Lupski, Jordan S Orange
Human NK cell deficiencies are rare yet result in severe and often fatal disease, particularly as a result of viral susceptibility. NK cells develop from hematopoietic stem cells, and few monogenic errors that specifically interrupt NK cell development have been reported. Here we have described biallelic mutations in IRF8, which encodes an interferon regulatory factor, as a cause of familial NK cell deficiency that results in fatal and severe viral disease. Compound heterozygous or homozygous mutations in IRF8 in 3 unrelated families resulted in a paucity of mature CD56dim NK cells and an increase in the frequency of the immature CD56bright NK cells, and this impairment in terminal maturation was also observed in Irf8-/-, but not Irf8+/-, mice...
November 28, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27893461/dual-modulation-of-mcl-1-and-mtor-determines-the-response-to-sunitinib
#5
Mohamed Elgendy, Amal Kamal Abdel-Aziz, Salvatore Lorenzo Renne, Viviana Bornaghi, Giuseppe Procopio, Maurizio Colecchia, Ravindran Kanesvaran, Chee Keong Toh, Daniela Bossi, Isabella Pallavicini, Jose Luis Perez-Gracia, Maria Dolores Lozano, Valeria Giandomenico, Ciro Mercurio, Luisa Lanfrancone, Nicola Fazio, Franco Nole, Bin Tean Teh, Giuseppe Renne, Saverio Minucci
Most patients who initially respond to treatment with the multi-tyrosine kinase inhibitor sunitinib eventually relapse. Therefore, developing a deeper understanding of the contribution of sunitinib's numerous targets to the clinical response or to resistance is crucial. Here, we have shown that cancer cells respond to clinically relevant doses of sunitinib by enhancing the stability of the antiapoptotic protein MCL-1 and inducing mTORC1 signaling, thus evoking little cytotoxicity. Inhibition of MCL-1 or mTORC1 signaling sensitized cells to clinically relevant doses of sunitinib in vitro and was synergistic with sunitinib in impairing tumor growth in vivo, indicating that these responses are triggered as prosurvival mechanisms that enable cells to tolerate the cytotoxic effects of sunitinib...
November 28, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27893460/tgf-%C3%AE-1-modulates-microglial-phenotype-and-promotes-recovery-after-intracerebral-hemorrhage
#6
Roslyn A Taylor, Che-Feng Chang, Brittany A Goods, Matthew D Hammond, Brian Mac Grory, Youxi Ai, Arthur F Steinschneider, Stephen C Renfroe, Michael H Askenase, Louise D McCullough, Scott E Kasner, Michael T Mullen, David A Hafler, J Christopher Love, Lauren H Sansing
Intracerebral hemorrhage (ICH) is a devastating form of stroke that results from the rupture of a blood vessel in the brain, leading to a mass of blood within the brain parenchyma. The injury causes a rapid inflammatory reaction that includes activation of the tissue-resident microglia and recruitment of blood-derived macrophages and other leukocytes. In this work, we investigated the specific responses of microglia following ICH with the aim of identifying pathways that may aid in recovery after brain injury...
November 28, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27869652/epithelial-to-mesenchymal-transition-drives-a-pro-metastatic-golgi-compaction-process-through-scaffolding-protein-paqr11
#7
Xiaochao Tan, Priyam Banerjee, Hou-Fu Guo, Stephen Ireland, Daniela Pankova, Young-Ho Ahn, Irodotos Michail Nikolaidis, Xin Liu, Yanbin Zhao, Yongming Xue, Alan R Burns, Jonathon Roybal, Don L Gibbons, Tomasz Zal, Chad J Creighton, Daniel Ungar, Yanzhuang Wang, Jonathan M Kurie
Tumor cells gain metastatic capacity through a Golgi phosphoprotein 3-dependent (GOLPH3-dependent) Golgi membrane dispersal process that drives the budding and transport of secretory vesicles. Whether Golgi dispersal underlies the pro-metastatic vesicular trafficking that is associated with epithelial-to-mesenchymal transition (EMT) remains unclear. Here, we have shown that, rather than causing Golgi dispersal, EMT led to the formation of compact Golgi organelles with improved ribbon linking and cisternal stacking...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27869651/pericyte-myd88-and-irak4-control-inflammatory-and-fibrotic-responses-to-tissue-injury
#8
Irina A Leaf, Shunsaku Nakagawa, Bryce G Johnson, Jin Joo Cha, Kristen Mittelsteadt, Kevin M Guckian, Ivan G Gomez, William A Altemeier, Jeremy S Duffield
Fibrotic disease is associated with matrix deposition that results in the loss of organ function. Pericytes, the precursors of myofibroblasts, are a source of pathological matrix collagens and may be promising targets for treating fibrogenesis. Here, we have shown that pericytes activate a TLR2/4- and MyD88-dependent proinflammatory program in response to tissue injury. Similarly to classic immune cells, pericytes activate the NLRP3 inflammasome, leading to IL-1β and IL-18 secretion. Released IL-1β signals through pericyte MyD88 to amplify this response...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27869650/inhibiting-mitochondrial-respiration-prevents-cancer-in-a-mouse-model-of-li-fraumeni-syndrome
#9
Ping-Yuan Wang, Jie Li, Farzana L Walcott, Ju-Gyeong Kang, Matthew F Starost, S Lalith Talagala, Jie Zhuang, Ji-Hoon Park, Rebecca D Huffstutler, Christina M Bryla, Phuong L Mai, Michael Pollak, Christina M Annunziata, Sharon A Savage, Antonio Tito Fojo, Paul M Hwang
Li-Fraumeni syndrome (LFS) is a cancer predisposition disorder caused by germline mutations in TP53 that can lead to increased mitochondrial metabolism in patients. However, the implications of altered mitochondrial function for tumorigenesis in LFS are unclear. Here, we have reported that genetic or pharmacologic disruption of mitochondrial respiration improves cancer-free survival in a mouse model of LFS that expresses mutant p53. Mechanistically, inhibition of mitochondrial function increased autophagy and decreased the aberrant proliferation signaling caused by mutant p53...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27869649/randomized-trial-of-calcipotriol-combined-with-5-fluorouracil-for-skin-cancer-precursor-immunotherapy
#10
Trevor J Cunningham, Mary Tabacchi, Jean-Pierre Eliane, Sara Moradi Tuchayi, Sindhu Manivasagam, Hengameh Mirzaalian, Ahu Turkoz, Raphael Kopan, Andras Schaffer, Arturo P Saavedra, Michael Wallendorf, Lynn A Cornelius, Shadmehr Demehri
BACKGROUND: Actinic keratosis is a precursor to cutaneous squamous cell carcinoma. Long treatment durations and severe side effects have limited the efficacy of current actinic keratosis treatments. Thymic stromal lymphopoietin (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity in barrier-defective skin. Here, we investigated the efficacy of calcipotriol, a topical TSLP inducer, in combination with 5-fluorouracil (5-FU) as an immunotherapy for actinic keratosis...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27869648/hippo-signaling-interactions-with-wnt-%C3%AE-catenin-and-notch-signaling-repress-liver-tumorigenesis
#11
Wantae Kim, Sanjoy Kumar Khan, Jelena Gvozdenovic-Jeremic, Youngeun Kim, Jason Dahlman, Hanjun Kim, Ogyi Park, Tohru Ishitani, Eek-Hoon Jho, Bin Gao, Yingzi Yang
Malignant tumors develop through multiple steps of initiation and progression, and tumor initiation is of singular importance in tumor prevention, diagnosis, and treatment. However, the molecular mechanism whereby a signaling network of interacting pathways restrains proliferation in normal cells and prevents tumor initiation is still poorly understood. Here, we have reported that the Hippo, Wnt/β-catenin, and Notch pathways form an interacting network to maintain liver size and suppress hepatocellular carcinoma (HCC)...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27906693/believe-the-miracles-of-biomedical-science-and-human-suffering
#12
Levi A Garraway
No abstract text is available yet for this article.
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27906692/introduction-of-peter-agre
#13
Paul B Rothman
No abstract text is available yet for this article.
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27906691/why-societies
#14
Daniel J DelloStritto
No abstract text is available yet for this article.
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27906690/the-long-road-to-leptin
#15
Jeffrey Friedman
Leptin is an adipose tissue hormone that functions as an afferent signal in a negative feedback loop that maintains homeostatic control of adipose tissue mass. This endocrine system thus serves a critical evolutionary function by protecting individuals from the risks associated with being too thin (starvation) or too obese (predation and temperature dysregulation). Mutations in leptin or its receptor cause massive obesity in mice and humans, and leptin can effectively treat obesity in leptin-deficient patients...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27906689/a-conversation-with-bruce-alberts
#16
Ushma S Neill
No abstract text is available yet for this article.
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27841765/macrophages-come-to-mind-as-keys-to-cognitive-decline
#17
D G Harrison, Tomasz J Guzik
Cognitive impairment, an underappreciated consequence of hypertension, is linked to cerebral arteriolar disease through poorly defined mechanisms. A study by Faraco et al. in this issue of the JCI points to perturbations of neurovascular unit coupling caused by perivascular macrophages (PVMs) as a cause of hypertension-related cognitive impairment. Angiotensin II (Ang II) was shown to activate PVMs, causing them to produce superoxide and thereby alter the proper functioning of the adjacent arterioles. Faraco and colleagues also show that disruption of the blood-brain barrier occurs in hypertension, allowing circulating Ang II to access PVMs...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27841764/antibody-drug-conjugate-targeting-cd46-eliminates-multiple-myeloma-cells
#18
Daniel W Sherbenou, Blake T Aftab, Yang Su, Christopher R Behrens, Arun Wiita, Aaron C Logan, Diego Acosta-Alvear, Byron C Hann, Peter Walter, Marc A Shuman, Xiaobo Wu, John P Atkinson, Jeffrey L Wolf, Thomas G Martin, Bin Liu
Multiple myeloma is incurable by standard approaches because of inevitable relapse and development of treatment resistance in all patients. In our prior work, we identified a panel of macropinocytosing human monoclonal antibodies against CD46, a negative regulator of the innate immune system, and constructed antibody-drug conjugates (ADCs). In this report, we show that an anti-CD46 ADC (CD46-ADC) potently inhibited proliferation in myeloma cell lines with little effect on normal cells. CD46-ADC also potently eliminated myeloma growth in orthometastatic xenograft models...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27841763/perivascular-macrophages-mediate-the-neurovascular-and-cognitive-dysfunction-associated-with-hypertension
#19
Giuseppe Faraco, Yukio Sugiyama, Diane Lane, Lidia Garcia-Bonilla, Haejoo Chang, Monica M Santisteban, Gianfranco Racchumi, Michelle Murphy, Nico Van Rooijen, Joseph Anrather, Costantino Iadecola
Hypertension is a leading risk factor for dementia, but the mechanisms underlying its damaging effects on the brain are poorly understood. Due to a lack of energy reserves, the brain relies on continuous delivery of blood flow to its active regions in accordance with their dynamic metabolic needs. Hypertension disrupts these vital regulatory mechanisms, leading to the neuronal dysfunction and damage underlying cognitive impairment. Elucidating the cellular bases of these impairments is essential for developing new therapies...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27841762/i-ve-got-algorithm-predicting-tumor-and-autoimmune-peptide-targets-for-cd8-t-cells
#20
Devin Dersh, Jonathan W Yewdell
CD8+ T cells play a central role in eradicating intracellular pathogens, but also are important for noninfectious diseases, including cancer and autoimmunity. The ability to clinically manipulate CD8+ T cells to target cancer and autoimmune disease is limited by our ignorance of relevant self-peptide target antigens. In this issue of the JCI, Pearson et al. describe 25,270 MHC class I-associated peptides presented by a wide range of HLA A and B allomorphs expressed by 18 different B cell lines. Via extensive bioinformatic analysis, the authors make surprising conclusions regarding the selective nature of peptide generation at the level of individual gene products and create a predictive algorithm for disease-relevant self-peptides that will be of immediate use for clinical and basic immunological research...
December 1, 2016: Journal of Clinical Investigation
journal
journal
27305
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"