tbuckley/cabot-search huggingface dataset:
Carbon black nanoparticles induce cell necrosis through lysosomal membrane permeabilization and cause subsequent inflammatory response
Authors: Xia Yuan, Wen Nie, Zhiyao He, Jingyun Yang, Bin Shao, Xuelei Ma, Xiangxian Zhang, Zhenfei Bi, Lu Sun, Xiao Liang, Yan Tie, Yu Liu, Fei Mo, Dan Xie, Yuquan Wei, Xiawei Wei
Journal: Theranostics (2020)

Rationale: The adverse health effects of nano-particulate pollutants have attracted much attention in recent years. Carbon nanomaterials are recognized as risk factors for prolonged inflammatory responses and diffuse alveolar injury. Previous research indicated a central role of alveolar macrophages in the pathogenesis of particle-related lung disease, but the underlying mechanism remains largely unknown. Methods: C57BL/6 mice were intratracheally instilled with carbon black nanoparticles (CBNPs). Cell necrosis and the infiltrated neutrophils in the lungs were detected by flow cytometry. Release of mitochondria was observed with Mito Tracker and mitochondrial DNA (mtDNA) was quantified by qPCR via Taqman probes. TLR9-p38 MAPK signaling pathway was detected by Western blotting. The production of lipid chemoattractant leukotriene B4 (LTB4) in the supernatant and bronchoalveolar lavage fluid (BALF) was quantitated using an enzyme immunoassay (EIA). Results: In the present study, we found that a single instillation of CBNPs induced neutrophil influx in C57BL/6 mice as early as 4 h post-exposure following the rapid appearance of cell damage indicators in BALF at 30 min. Macrophages exposed to CBNPs showed necrotic features and were characterized by lysosome rupture, cathepsin B release, reactive oxygen species generation, and reduced intracellular ATP level. Necrosis was partly inhibited by a specific lysosomal cathepsin B inhibitor CA074 Me. Further analyses suggested that the resulting leakage of mtDNA from the necrotic cells activated neutrophils and triggered severe inflammation in vivo. Pulmonary neutrophilic inflammation induced by mtDNA was reduced in TLR9-/- mice. Additionally, mtDNA induced LTB4 production from macrophages, which may contribute to neutrophil recruitment. Conclusion: We demonstrated here that CBNPs induce acute cell necrosis through lysosomal rupture and that mtDNA released from necrotic cells functions as a key event mediating pulmonary neutrophilic inflammation. This study described a novel aspect of the pathogenesis of particle-induced inflammatory response and provided a possible therapeutic target for the regulation of inflammation.
Multimodel preclinical platform predicts clinical response of melanoma to immunotherapy
Authors: Eva Pérez-Guijarro, Howard H. Yang, Romina E. Araya, Rajaa El Meskini, Helen T. Michael, Suman Kumar Vodnala, Kerrie L. Marie, Cari Smith, Sung Chin, Khiem C. Lam, Andres Thorkelsson, Anthony J. Iacovelli, Alan Kulaga, Anyen Fon, Aleksandra M. Michalowski, Willy Hugo, Roger S. Lo, Nicholas P. Restifo, Shyam K. Sharan, Terry Van Dyke, Romina S. Goldszmid, Zoe Weaver Ohler, Maxwell P. Lee, Chi-Ping Day, Glenn Merlino
Journal: Nature Medicine (2020)
Safety, tolerability, pharmacokinetics, and antimalarial efficacy of a novel Plasmodium falciparum ATP4 inhibitor SJ733: a first-in-human and induced blood-stage malaria phase 1a/b trial
Authors: Aditya H Gaur, James S McCarthy, John C Panetta, Ronald H Dallas, John Woodford, Li Tang, Amber M Smith, Tracy B Stewart, Kristen C Branum, Burgess B Freeman, Nehali D Patel, Elizabeth John, Stephan Chalon, Shelley Ost, Ryan N Heine, Julie L Richardson, Robbin Christensen, Patricia M Flynn, Yvonne Van Gessel, Branko Mitasev, Jörg J Möhrle, Fabian Gusovsky, Lidiya Bebrevska, R Kiplin Guy
Journal: The Lancet Infectious Diseases (2020)
<i>In vivo</i> assessment of inflammation in carotid atherosclerosis by noninvasive photoacoustic imaging
Authors: Zhihua Xie, Yanqing Yang, Yaqiong He, Chengyou Shu, Dong Chen, Jinke Zhang, Jingqin Chen, Chengbo Liu, Zonghai Sheng, Huadong Liu, Jie Liu, Xiaojing Gong, Liang Song, Shaohong Dong
Journal: Theranostics (2020)

Objectives:The objective of this study was to demonstrate the feasibility of using noninvasive photoacoustic imaging technology along with novel semiconducting polymer nanoparticles for in vivo identifying inflammatory components in carotid atherosclerosis and assessing the severity of inflammation using mouse models.Methods and Results: Healthy carotid arteries and atherosclerotic carotid arteries were imaged in vivo by the noninvasive photoacoustic imaging system.Molecular probes PBD-CD36 were used to label the inflammatory cells to show the inflammation information by photoacoustic imaging.In in vivo imaging experiments, we observed the maximum photoacoustic signal enhancement of 4.3, 5.2, 8 and 16.3 times between 24 h post probe injection and that before probe injection in four carotid arteries belonging to three atherosclerotic mice models.In the corresponding carotid arteries stained with CD36, the ratio of 0.043, 0.061, 0.082 and 0.113 was found between CD36 positive (CD36(+)) expression area and intima-media area (P < 0.05).For the CD36(+) expression less than 0.008 in eight arteries, no photoacoustic signal enhancement was found due to the limited system sensitivity.The photoacoustic signal reflects CD36(+) expression in plaques, which shows the feasibility of using photoacoustic imaging for in vivo assessment of carotid atherosclerosis. Conclusion:This research demonstrates a semiconducting polymer nanoparticle along with photoacoustic technology for noninvasive imaging and assessment of inflammation of carotid atherosclerotic plaques in vivo.
Advice for Clinicians on How to Treat Comorbid Anxiety and Depression
Authors: Jan Spijker, Anna Muntingh, Neeltje Batelaan
Journal: JAMA Psychiatry (2020)

Depressive and anxiety disorders frequently co-occur. It is widely known that the outcome of comorbid anxiety and depressive disorder together is more negative than each single counterpart. Clinically, comorbidity is associated with greater severity of symptoms, with an increased risk of suicide, a more reduced quality of life, and a more limited level of functioning. Although it can be questioned whether it is best to view depression and anxiety as a single condition or distinct conditions, current clinical practice is to diagnose both disorders separately and refer to comorbidity. However, a clear-cut optimal treatment strategy for comorbid anxiety and depression is lacking. Should we treat the disorders sequentially (treating one and subsequently the other) or parallel (treating both disorders simultaneously)? Should we start a single treatment focusing on both disorders (integrated treatment) or a transdiagnostic treatment focusing on underlying mechanisms present in both anxiety and depressive disorders?
Chemosensory Cell-Derived Acetylcholine Drives Tracheal Mucociliary Clearance in Response to Virulence-Associated Formyl Peptides
Authors: Alexander Perniss, Shuya Liu, Brett Boonen, Maryam Keshavarz, Anna-Lena Ruppert, Thomas Timm, Uwe Pfeil, Aichurek Soultanova, Soumya Kusumakshi, Lucas Delventhal, Öznur Aydin, Martina Pyrski, Klaus Deckmann, Torsten Hain, Nadine Schmidt, Christa Ewers, Andreas Günther, Günter Lochnit, Vladimir Chubanov, Thomas Gudermann, Johannes Oberwinkler, Jochen Klein, Katsuhiko Mikoshiba, Trese Leinders-Zufall, Stefan Offermanns, Burkhard Schütz, Ulrich Boehm, Frank Zufall, Bernd Bufe, Wolfgang Kummer
Journal: Immunity (2020)

Mucociliary clearance through coordinated ciliary beating is a major innate defense removing pathogens from the lower airways, but the pathogen sensing and downstream signaling mechanisms remain unclear. We identified virulence-associated formylated bacterial peptides that potently stimulated ciliary-driven transport in the mouse trachea. This innate response was independent of formyl peptide and taste receptors but depended on key taste transduction genes. Tracheal cholinergic chemosensory cells expressed these genes, and genetic ablation of these cells abrogated peptide-driven stimulation of mucociliary clearance. Trpm5-deficient mice were more susceptible to infection with a natural pathogen, and formylated bacterial peptides were detected in patients with chronic obstructive pulmonary disease. Optogenetics and peptide stimulation revealed that ciliary beating was driven by paracrine cholinergic signaling from chemosensory to ciliated cells operating through muscarinic M3 receptors independently of nerves. We provide a cellular and molecular framework that defines how tracheal chemosensory cells integrate chemosensation with innate defense.
Inesa Benedictovna Kozlovskaya: expert on motor control and space medicine
Authors: Elena Tomilovskaya, Boleslav Lichterman
Journal: BMJ (2020)

Inesa Benedictovna Kozlovskaya was born in Harbin in China. Her father, Benedict (Benecian) Kozlovsky, administered the Soviet consulate. In 1938 the family moved to Moscow and in 1945 Kozlovskaya became a student at the First Moscow Medical Institute (now the IM Sechenov First Moscow State Medical University). On graduating she entered a doctorate programme at the department of normal physiology, and in 1955 defended her dissertation, On the Impact of Higher Parts of Nervous System on Morphological Composition of Blood in Animals. She then worked as an assistant professor at the department under the guidance of the Soviet physiologists Piotr Anokhin and Mikhail Usievich. In 1959 she moved to the Institute of Higher Nervous Activity and worked at the laboratory of Georgy Skipin, who studied instrumental conditioning. Skipin was a friend of Jerzy Konorski from the Nencki Institute of Experimental Biology in Warsaw.

Despite the cold war, a programme of academic exchange between the Soviet Union and the USA had been running since the 1960s. In …
Lown-Ganong-Levine Syndrome
Authors: WILLIAM J. MANDEL, RONALD DANZIG, H. HAYAKAWA
Journal: Circulation (1971)

His bundle recordings were obtained in three patients with histories of recurrent supraventricular tachycardias and electrocardiograms demonstrating a short P-R interval with a normal QRS (the Lown-Ganong-Levine syndrome). The His bundle electrograms obtained during sinus rhythm demonstrated a normal A-H (atrium-to-His bundle) time in one patient and a low normal A-H time in two patients. The H-V (His bundle-to-ventricle) time was short in all three patients. Atrial pacing in two patients produced an attenuated degree of prolongation of the A-H time without a change in conduction distal to the proximal His bundle. The probable mechanisms of accelerated conduction in these three patients include: (1) partial A-V nodal bypass via (a) the posterior intenodal tract or (b) functional bypass fibers within the A-V node; and (2) accelerated conduction within the A-V conduction system distal to the A-V node.
Role of Histamine in Hypoxic Pulmonary Hypertension in the Rat
Authors: ANTON HAUGE, KENNETH L. MELMON
Journal: Circulation Research (1968)

The present investigation was undertaken to see if any of the naturally occurring vasoactive substances was likely to act as a mediator for the pulmonary vasoconstrictor response to acute alveolar hypoxia. Rats were treated with agents that deplete local stores of vasoactive amines or inhibit their synthesis. Lungs from these animals were isolated, ventilated, and perfused with homologous blood at constant volume inflow. Their pressor responses to 2- to 3-minute periods of ventilation hypoxia (2% O 2 ) were observed. The histamine-releasing agent 48/80 or the histidine decarboxylase inhibitor NSD 1055, or both, depleted 73% of the histamine in the lung but had no consistent effect on the pressor responses to hypoxia. When 48/80 (0.2 to 1 mg) was given in vitro, histamine in the lung was reduced to 10% of normal, or less, and the pressor response to alveolar hypoxia was completely abolished. Reserpine, guanethidine, or alpha-methyl-tyrosine reduced catecholamine stores in heart tissue (as an index of general tissue changes) by a maximum of 90% and reserpine decreased serotonin in the lung by 93% without inhibiting the hypoxic pressor responses. The findings strengthen the concept that histamine mediates the pressor response to acute alveolar hypoxia in the rat.
Sustained mitochondrial biogenesis is essential to maintain caloric restriction-induced beige adipocytes
Authors: Raja Gopal Reddy Mooli, Dhanunjay Mukhi, Mikayla Watt, Lia Edmunds, Bingxian Xie, Joseph Capooci, Matthew Reslink, Chetachukwu Eze, Amanda Mills, Donna B. Stolz, Michael Jurczak, Sadeesh K. Ramakrishnan
Journal: Metabolism (2020)
Heart Failure Outcomes and Associated Factors Among Veterans With Human Immunodeficiency Virus Infection
Authors: Sebhat Erqou, Lan Jiang, Gaurav Choudhary, Michelle Lally, Gerald S Bloomfield, Andrew R Zullo, Theresa I Shireman, Mathew Freiberg, Amy C Justice, James Rudolph, Nina Lin, Wen-Chih Wu
Journal: JACC Heart Failure (2020)
Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation
Authors: Erik C. B. Johnson, Eric B. Dammer, Duc M. Duong, Lingyan Ping, Maotian Zhou, Luming Yin, Lenora A. Higginbotham, Andrew Guajardo, Bartholomew White, Juan C. Troncoso, Madhav Thambisetty, Thomas J. Montine, Edward B. Lee, John Q. Trojanowski, Thomas G. Beach, Eric M. Reiman, Vahram Haroutunian, Minghui Wang, Eric Schadt, Bin Zhang, Dennis W. Dickson, Nilüfer Ertekin-Taner, Todd E. Golde, Vladislav A. Petyuk, Philip L. De Jager, David A. Bennett, Thomas S. Wingo, Srikant Rangaraju, Ihab Hajjar, Joshua M. Shulman, James J. Lah, Allan I. Levey, Nicholas T. Seyfried
Journal: Nature Medicine (2020)
A Guide to the Clinical Examination and Treatment of Sick Children.
Journal: JAMA (1898)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
STAT3 Activation-Induced Fatty Acid Oxidation in CD8
Authors: Chunyan Zhang, Chanyu Yue, Andreas Herrmann, Jieun Song, Colt Egelston, Tianyi Wang, Zhifang Zhang, Wenzhao Li, Heehyoung Lee, Maryam Aftabizadeh, Yi Jia Li, Peter P Lee, Stephen Forman, George Somlo, Peiguo Chu, Laura Kruper, Joanne Mortimer, Dave S B Hoon, Wendong Huang, Saul Priceman, Hua Yu
Journal: Cell Metabolism (2019)
Level of Tumor Necrosis Factor Production by Stimulated Blood Mononuclear Cells Can Be Used to Predict Response of Patients With Inflammatory Bowel Diseases to Infliximab
Authors: Bosse Jessen, Yasmina Rodriguez-Sillke, Elena Sonnenberg, Michael Schumann, Andrey Kruglov, Inka Freise, Franziska Schmidt, Jochen Maul, Anja A. Kühl, Rainer Glauben, Donata Lissner, Britta Siegmund
Journal: Clinical Gastroenterology and Hepatology (2020)
Extracellular vesicles from human umbilical cord blood plasma modulate interleukin-2 signaling of T cells to ameliorate experimental autoimmune encephalomyelitis
Authors: Sueon Kim, Ji-young Maeng, Seung-Joo Hyun, Hyun-Jung Sohn, Su-Yeon Kim, Cheol-Hwa Hong, Tai-Gyu Kim
Journal: Theranostics (2020)

Human umbilical cord blood (UCB) cell-derived extracellular vesicles (EV) reportedly play immunosuppressive roles; however, UCB plasma-derived extracellular vesicles (CBP EVs) remain poorly studied. We examined the immunosuppressive potential of CBP EVs compared to that of adult blood plasma-derived extracellular vesicles (ABP EVs) in vitro and constructed an experimental autoimmune encephalomyelitis (EAE) model. Methods: CBP EVs were isolated by ultracentrifugation and their proteomic profiling was performed using the high-resolution liquid chromatography with tandem mass spectrometry. Human T lymphocytes or mouse splenocytes labeled with carboxyfluorescein succinimidyl ester were incubated with CBP EV to measure the immunosuppressive function of CBP EV. The effect on T-cell polarization was analyzed by flow cytometry and enzyme-linked immunospot assay. The matrix metalloproteinase (MMP) function in CBP EV was specifically inhibited using a chemical inhibitor. The efficacy of CBP EVs in the EAE mouse model was determined by scoring the symptoms and analyzing cell phenotype and cytokines using mouse splenocytes. We generated genetically engineered artificial EVs using HLA/MIC-null HEK293T (H1ME-5) cell line to characterize the immunosuppressive effect of CBP EV. Results: CBP EVs primarily inhibited the proliferation of T cells by reducing the production of IL-2. Specifically, CBP EV-derived matrix metallopeptidase cleaved the IL-2 receptor α (CD25) on the surface of activated T cells, consequently downregulating IL-2 signaling in response to IL-2R engagement. Although the inhibition of MMP activity in CBP EVs abrogated CD25 cleavage and restored IL-2 production in activated T cells, the immunosuppressive response was not fully recovered. Thus, we further analyzed changes in immunosuppressive cells such as regulatory T cells and bone marrow-derived suppressor cells by CBP EV. Further, GAL-3, GAL-7, S100-A7, MMP-9, MMP-8, HSP-72, and PIP were highly enriched in CBP EV-mimics in which they served as pivotal mediators of CBP EV-induced immunosuppressive effects. Therefore, we generated genetically engineered GAL-3, GAL-7, S100-A7, MMP-9, MMP-8, HSP-72, and PIP-EVs using HLA/MIC-null HEK293T cells to characterize the immunosuppressive effect of these molecules. Among these, MMP-9 and HSP-72-enriched EVs showed the most significant T cell immunosuppression. Conclusion: CBP EVs inhibited T cell proliferation and EAE development by modulating IL-2 signaling and immunosuppressive cell fate. CBP EVs contain critical components for immunosuppression and that CBP EV mimics, specifically those expressing MMP-9 and HSP-72, may offer a novel promising strategy for the treatment of various autoimmune diseases.
Bronchodilator responsiveness in children with cystic fibrosis and allergic bronchopulmonary aspergillosis
Authors: Mordechai Pollak, Michelle Shaw, David Wilson, Hartmut Grasemann, Felix Ratjen
Journal: European Respiratory Journal (2020)

<b>CF patients with a new diagnosis of ABPA had a similar BD response, compared to CF patients with acute lung function deterioration from other causes. BD response testing did not help differentiating ABPA from other causes of lung function deterioration.</b>https://bit.ly/39Oegnh
Identification of a founder mutation in <i> <scp>KRT</scp> 14 </i> associated with Naegeli–Franceschetti–Jadassohn syndrome
Authors: D.J. Ralser, S. Kumar, O. Borisov, O. Sarig, G. Richard, S. Wolf, P.M. Krawitz, E. Sprecher, M. Kreiß, R.C. Betz
Journal: British Journal of Dermatology (2020)
Neurologic Features in Severe SARS-CoV-2 Infection
Authors: Julie Helms, Stephane Kremer, Hamid Merdji, Raphaël Clere-Jehl, Malika Schenck, Christine Kummerlen, Olivier Collange, Clotilde Boulay, Samira Fafi-Kremer, Mickaël Ohana, Mathieu Anheim, Ferhat Meziani
Journal: New England Journal of Medicine (2020)

Neurologic Features in SARS-CoV-2 Infection In a consecutive series of 64 patients with Covid-19 and ARDS, 58 of whom underwent neurologic examination, severe agitation and corticospinal signs were...
Catheterization and Mortality in Elderly Patients With Acute Myocardial Infarction
Authors: Kathryn Davis
Journal: JAMA (1995)

<h3>To the Editor.</h3> —In their analysis of intensive treatment of AMI, Dr McClellan and colleagues<sup>1</sup>warn us about the potential biases in the use of nonexperimental data for outcomes research. They have introduced an interesting methodology that is new to outcomes research; however, I believe they have made an important methodological error in their own analysis. In Table 1, the mortality rates for groups of patients with and without catheterization are given for 1-, 7-, and 30-day periods and for 1, 2, 3, and 4 years. These simple rates are misleading because the categorization factor (catheterization within 90 days) and the outcome (death) are not independent since patients will not have catheterization after they die. For example, most patients who died on day 1 are in the group without catheterization because catheterization is not often performed very early in the course of an AMI. Patients had to have catheterization
Legionnaires Disease Death Linked to Home Water Contamination
Authors: Bridget M. Kuehn
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
ACKR4 restrains antitumor immunity by regulating CCL21
Authors: Carly E. Whyte, Maleika Osman, Ervin E. Kara, Caitlin Abbott, Jade Foeng, Duncan R. McKenzie, Kevin A. Fenix, Yuka Harata-Lee, Kerrie L. Foyle, Sarah T. Boyle, Marina Kochetkova, Amelia Roman Aguilera, Jiajie Hou, Xian-Yang Li, Mark A. Armstrong, Stephen M. Pederson, Iain Comerford, Mark J. Smyth, Shaun R. McColl
Journal: The Journal of Experimental Medicine (2020)

Current immunotherapies involving CD8+ T cell responses show remarkable promise, but their efficacy in many solid tumors is limited, in part due to the low frequency of tumor-specific T cells in the tumor microenvironment (TME). Here, we identified a role for host atypical chemokine receptor 4 (ACKR4) in controlling intratumor T cell accumulation and activation. In the absence of ACKR4, an increase in intratumor CD8+ T cells inhibited tumor growth, and nonhematopoietic ACKR4 expression was critical. We show that ACKR4 inhibited CD103+ dendritic cell retention in tumors through regulation of the intratumor abundance of CCL21. In addition, preclinical studies indicate that ACKR4 and CCL21 are potential therapeutic targets to enhance responsiveness to immune checkpoint blockade or T cell costimulation.