tbuckley/cabot-search huggingface dataset:
The immune suppressive microenvironment of human gliomas depends on the accumulation of bone marrow-derived macrophages in the center of the lesion
Authors: Laura Pinton, Elena Masetto, Marina Vettore, Samantha Solito, Sara Magri, Marta D’Andolfi, Paola Del Bianco, Giovanna Lollo, Jean-Pierre Benoit, Hideho Okada, Aaron Diaz, Alessandro Della Puppa, Susanna Mandruzzato
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Systemic and local immune suppression plays a significant role in glioma progression. Glioma microenvironment contains both brain-resident microglial cells (MG) and bone marrow-derived macrophages (BMDM), but the study of their functional and immune regulatory activity has been hampered until now by the lack of markers allowing a proper identification and isolation to collect pure populations. <h3>Methods</h3> Myeloid and lymphoid infiltrate were characterized in grade II, III and IV gliomas by multicolor flow cytometry, along with the composition of the cell subsets of circulating myeloid cells. Macrophages were sorted and tested for their immunosuppressive ability. Moreover, following preoperative administration of 5-aminolevulinic acid to patients, distinct areas of tumor lesion were surgically removed and analyzed, based on protoporphyrin IX fluorescence emission. <h3>Results</h3> The immune microenvironment of grade II to grade IV gliomas contains a large proportion of myeloid cells and a small proportion of lymphocytes expressing markers of dysfunctional activity. BMDM and resident MG cells were characterized through a combination of markers, thus permitting their geographical identification in the lesions, their sorting and subsequent analysis of the functional characteristics. The infiltration by BMDM reached the highest percentages in grade IV gliomas, and it increased from the periphery to the center of the lesion, where it exerted a strong immunosuppression that was, instead, absent in the marginal area. By contrast, MG showed little or no suppression. Functional differences, such as iron metabolism and phagocytosis, characterized resident versus blood-derived macrophages. Significant alterations in circulating monocytes were present in grade IV patients, correlating with accumulation of tumor macrophages. <h3>Conclusions</h3> Grade IV gliomas have an alteration in both circulating and tumor-associated myeloid cells and, differently from grade II and III gliomas, show a significant presence of blood-derived, immune suppressive macrophages. BMDM and MG have different functional properties.
Abstract 15428: Crucial Role of ROCK1 to Maintain Contractile Cardiac Function in Response to Chronic Pressure-Overload in Mice
Authors: Shinichiro Sunamura, Kimio Satoh, Kota Suzuki, Shun Kudo, Shohei Ikeda, Kikuchi Nobuhiro, Omura Junichi, Taijyu Satoh, Ryo Kurosawa, Masamichi Nogi, Kazuhiko Numano, Toru Shimizu, Hiroaki Shimokawa
Journal: Circulation (2016)

Background: Rho-kinase plays a crucial role in the development of cardiac hypertrophy and failure. There are 2 isoforms of Rho-kinase, ROCK1 and ROCK2, with different functions in cardiac tissues (e.g. ECs, VSMCs, cardiomyocytes and cardiac fibroblasts). It has been demonstrated that ROCK2 in cardiomyocytes promotes cardiac hypertrophy and fibrosis in response to pressure-overload. However, the specific roles of ROCK1 in cardiomyocytes remain to be elucidated. Methods and Results: We newly generated cardiac-specific ROCK1-deficient (KO) mice by Cre-loxP system. We performed transverse aortic constriction (TAC) in wild-type (WT) and ROCK1-KO mice and thereafter examined the time-course for 4 weeks. Importantly, the time-course and localization of ROCK1 and ROCK2 expression after TAC were completely different in WT hearts; ROCK2 was up-regulated in the left ventricular (LV) free wall and ROCK1 in the coronary arterial wall and perivascular area at day7. Western blotting of WT hearts also demonstrated signif...
Oxymatrine therapy inhibited epidermal cell proliferation and apoptosis in severe plaque psoriasis
Authors: H.‐J. Shi, H. Zhou, A.‐L. Ma, L. Wang, Q. Gao, N. Zhang, H.‐B. Song, K.‐P. Bo, W. Ma
Journal: British Journal of Dermatology (2019)

Psoriasis is a chronic skin disorder that manifests as epidermal keratinocyte hyperplasia. We examined the effect of oxymatrine treatment on cell proliferation and apoptosis in skin lesions of psoriasis. Patients with severe plaque psoriasis were treated with oxymatrine or with acitretin. The skin lesions were stained with proliferating cell nuclear antigen (PCNA), Ki‐67 and Bcl‐2, as well as examined by terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling (TUNEL). We performed correlations of the Psoriasis Area and Severity Index (PASI) and the proliferation and apoptosis index. Oxymatrine significantly reduced the psoriasis lesions as demonstrated by the reduced PASI score after treatment [6·91; 95% confidence interval (CI) 5·00–8·81, P < 0·001]. In the oxymatrine group, the mitotic index was 26·15 (95% CI 24·80–27·49) before oxymatrine treatment, decreasing to 14·52 (95% CI 13·82–15·25; P < 0·001) after treatment, but remained higher than the normal group (6·24; 95% CI 5·87–6·61, P < 0·001). Oxymatrine also inhibited the proliferation of epidermal cells in the skin lesion as indicated by the reduced proliferation index after treatment (P < 0·01). In addition, oxymatrine treatment reduced cellular apoptosis as shown by increased Bcl‐2 expression and a decrease in TUNEL‐positive cells. The PASI score was positively correlated with mitotic index, proliferation index and apoptotic index (TUNEL), but negatively correlated with Bcl‐2 expression. Oxymatrine treatment reduced proliferation but inhibited apoptosis of cells in the skin lesion. The balance between cell proliferation and turnover may contribute to the significant alleviation of psoriasis by oxymatrine. What's already known about this topic? Psoriasis manifests as epidermal keratinocyte hyperplasia with proliferation, keratinocyte maturation and turnover rates. Current drugs for psoriasis may inhibit cell proliferation but could not adjust the balance of cell division, differentiation and apoptosis. What does this study add? We studied the efficacy of oxymatrine in the treatment of psoriasis and analysed the correlation of skin lesions, proliferation and apoptosis index before and after oxymatrine treatment. What is the translational message? Our study has demonstrated that oxymatrine is effective in the treatment of severe plaque psoriasis. It has comparable efficacy with acitretin. Because acitretin treatment was sometimes associated with metabolic abnormalities, our study suggests oxymatrine therapy as an alternative treatment for psoriasis in the context of acitretin allergy or adverse reactions.
Irish GP admits prescribing opioids inappropriately to feed his addiction
Authors: Clare Dyer
Journal: BMJ (2019)

Patients of an Irish GP are to be told for the first time that they were prescribed unnecessary opioids and that their doctor was administering some of the drugs to himself to feed his addiction.

The unnamed GP has admitted to the Medical Council of Ireland that over a five year period he administered opioids orally or intra-muscularly to one or more of 36 named patients, when he knew or ought to have known that it was “inappropriate or not clinically warranted.”

He also admitted prescribing opioids for one or more of six named patients “in excessive quantities or strengths” and taking unused vials for himself. …
POSTERIOR WALL ABLATION AS AN ADJUNCTIVE THERAPY TO PULMONARY VEIN ISOLATION REDUCES RECURRENCE OF ATRIAL FIBRILLATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Florentino Lupercio, Andrew Lin, Omar Aldaas, Gordon Ho, Farshad Raissi, Kurt Hoffmayer, Frederick Han, David Krummen, Gregory Feld, Jonathan Hsu
Journal: Journal of the American College of Cardiology (2019)
Abstract 351: Methylglyoxal Increases mTOR Activity Without Altering Autophagy in Animal Model of Acute Myocardial Infarction
Authors: Alessandra Machado, Bianca Fracasso, Juliana Rangel, Graziela Pinto, Niara Medeiros, Mariana Breidenbach, Daniel Caetano, Luiz Rohde, Andreia Biolo, Michael Andrades
Journal: Circulation Research (2018)

Methylglyoxal (MG) is a highly reactive small carbonyl that generates Advanced Glycation End-products (AGEs) and both compounds are increased during diabetes, myocardial infarction (MI), and in inflammatory diseases. MI can trigger autophagy, a mechanism of cellular recycling that generates energy in situations of nutrient deprivation. However, the benefit of autophagy when stimulated in the presence of AGEs is still not clear. Therefore, the objective of this study was to evaluate the role of methylglyoxal in the activation of autophagy and on cardiac remodeling. To this, 90 male Wistar rats were randomized into Sham, MI, and MI pretreated with MG (7 days, 75 mg/kg/day, twice a day) or rapamycin (24 and 4 hours, 8 mg/kg). Echocardiography was performed by a blinded researcher 24 hours after the surgery and soon after the animals were killed and samples were prepared for western blot. MG treatment did not increase AGEs in the heart tissue or impair ejection fraction, fractional shortening, and chamber remodeling assessed 24 hours after the MI. However, it caused a 9-fold increase in mTOR activation (p=0.02) without changing the content of autophagy related proteins (LC3II/I ratio and p62). Curiously, Rapamycin, a known activator of autophagy, did not prevent heart remodeling. In conclusion, the glycating agent MG given before MI increases mTOR signaling without affecting autophagy and does not alter cardiac remodeling. Financial support: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Incentivo à Pesquisa do Hospital de Clínicas de Porto Alegre (FIPE-HCPA), and Fundo de Amparo à Pesquisa do RS (Fapergs).
NHS England sets out plan to revoke Lansley’s competition rules
Authors: Gareth Iacobucci
Journal: BMJ (2019)

NHS England has outlined plans to repeal divisive laws on competition and procurement that were introduced in the Health and Social Care Act 2012 in a bid to promote integration in the health service.12

The move, which was trailed in the NHS long term plan,3 is designed to make it easier for the NHS to integrate services by freeing commissioners from the burden of having to tender service contracts on the open market.

If approved by ministers, the legislative change, which was recommended by the cross-party Commons health and social select committee, would mark a major shift away from the pro-competition agenda championed by former health secretary Andrew Lansley, the architect of the 2012 act.

The rules governing competition in …
Abstract 319: Mir-222 is Required for Physiological Hypertrophy but Inhibits Pathological Hypertrophy and Heart Failure
Authors: Xiaojun Liu, Haobo Li, Chunyang Xiao, Federico Damilano, Colin Platt, Carolin Lerchunmuller, Han Zhu, Paul Wei, Ashish Yeri, Patrick Most, Anthony Rosenzweig
Journal: Circulation Research (2018)

Background: Physiological cardiac hypertrophy occurs commonly in response to exercise and can protect against pathological stress. In contrast, pathological hypertrophy occurs in disease and often precedes heart failure . Although physiological and pathological hypertrophy often involve distinct signaling mechanisms, miR-222 is an exercise-induced microRNA that is required for physiological hypertrophy but is also induced in pathological hypertrophy. Here, we sought to define the role of miR-222 in pathological hypertrophy. Methods and Results: We generated miR-222 gain-of-function (GOF) models through cardiac-specific constitutive transgenic miR-222 expression (TgC-miR-222) or somatic expression with AAV9-miR-222. Loss-of-function (LOF) was achieved using a locked nucleic antimiR (LNA) specific for miR-222. miR-222 GOF and LOF models manifested normal cardiac structure and function at baseline. After transverse aortic constriction (TAC), TgC-miR-222 had less pathological hypertrophy as well as better cardiac function (FS = 37.9% vs 28.7%, p&lt;0.01) and survival (median survival = 120 days vs 54 days, p&lt;0.05). Similarly, AAV9-miR-222 gene transfer immediately after TAC also better preserved cardiac function. Conversely, LNA-anti-miR-222 dramatically exacerbated pathological hypertrophy, cardiac dysfunction, and heart failure (FS = 24.4% vs 35.3%, p&lt;0.01) after TAC. PUMA, a pro-apoptotic Bcl-2 family member and two transcription factors, Hmbox1 and NFATc3, were identified as novel, direct miR-222 targets contributing to its roles in this context. Conclusions: Although miR-222 is upregulated in both physiological and pathological hypertrophy, its roles in these conditions are quite different. In response to pressure overload, miR-222 inhibits pathological hypertrophy, adverse remodeling, and cardiac dysfunction. These findings reinforce the conceptual model that physiological and pathological hypertrophy are qualitatively distinct, rather than differing only in degree. Further, they suggest that miR-222 may hold promise as a potential therapeutic target in pathological cardiac hypertrophy and heart failure.
THE INCREMENTAL ROLE OF IMAGING IN THROMBOEMBOLIC RISK ASSESSMENT FOR PATIENTS WITH ATRIAL FIBRILLATION
Authors: Reza Reyaldeen, Karthik Nath, Dharmenaan Palamuthusingam, Jovita Dwivedi, Danielle Harrop, Arnold Ng, William Wang
Journal: Journal of the American College of Cardiology (2019)
Abstract 469: Transient Introduction of miR-294 in the Heart Promotes Cardiomyocyte Cell Reentry After Injury
Authors: Justin Kurian, Austin Borden, Constantine Troupes, Yijun Yang, Emily Nickoloff, Sadia Mohsin, Steven Houser, Raj Kishore, Mohsin Khan
Journal: Circulation Research (2018)

Rationale: Embryonic heart is characteristic of rapidly dividing cardiomyocytes required to build a working myocardium. Cardiomyocytes retain some proliferative capacity in the neonates but lose most of it in adulthood. Consequently, a number of signaling hubs including microRNAs are altered during cardiac development. Embryonic stem cell cycle (ESCC) miRs are a class of microRNAs exclusively expressed during developmental stages but their effect on cardiomyocyte proliferation and heart function has not been previously studied. Objective: To determine whether miR-294 promotes cardiomyocyte cell cycle reentry enhancing cardiac repair after myocardial infarction. Methods and Results: miR expression analysis in the heart during development revealed elevated levels of miR-294 in the prenatal stages but was lost in the neonate and adult heart as confirmed by qRT-PCR and in situ hybridization. Neonatal ventricular cardiomyocytes (NRVMs) treated with miR-294 mimic showed elevated expression of Ki67 (7-fold), p-histone 3 (7.5-fold) and Aurora B kinase (11.8 fold) as confirmed by immunocytochemistry compared to control cells. Similar results were confirmed in adult cardiomyocytes with p-histone staining and mRNA analysis. Moreover, miR-294 enhanced oxidative phosphorylation and glycolysis in NRVMs as measured by seahorse assay. Mechanistically, array analysis revealed upregulation of cell cycle markers including blunting of negative regulators as confirmed by qRT-pCR and immunoblot analysis. Next, an inducible miR-294 AAV-9-αMHC vector was delivered to mice fed dox chow for 2 wks following myocardial infarction. Increased EF, FS and hemodynamic parameters together with decreased infarct size and apoptosis was observed 8 wks after MI. Myocyte proliferation increased in miR-294 hearts analyzed by Ki67, p-H3 and AurB expression parallel to increase in small myocyte number in the heart. Isolated adult myocytes from miR-294 hearts showed increased EdU+ cells and upregulation of cell cycle markers/miR targets 8 wks after MI. Conclusion: Ectopic expression of miR-294 recapitulates developmental signaling and phenotype in cardiomyocyte promoting cell cycle reentry that leads to augmented cardiac function in mice after myocardial infarction.
LEFT VENTRICULAR MYOCARDIAL PERFUSION IMPROVES POST TRANSCATHETER AORTIC VALVE REPLACEMENT IN LOW-RISK POPULATION ASSESSED BY COMPUTED TOMOGRAPHY IMAGES
Authors: Jingyuan Ma, Federico Asch, Gaby Weissman, Fernando Rodriguez-Weisson, Toby Rogers, Paige E. Craig, Itsik Ben-Dor, Hector Garcia Garcia, Lowell Satler, Rebecca Torguson, Ron Waksman, Diego Medvedofsky
Journal: Journal of the American College of Cardiology (2019)
Transforming growth factor Β receptor typr II (TGFB RII) affects the sensitivity of colon cancer cell lines to 5- fluorouracil
Authors: Swati Biswas, Ron Rerko, Sandra Swinler, James K. Willson, Sanford D. Markowitz, William M. Grady
Journal: Cancer Research (2004)

5209  Background: We previously demonstrated mutational inactivation of type II TGF-β receptors (TGFBR2) occurs in approximately 30% of all colon cancers. In light of the frequency of TGFBR2 mutations in colon cancer and the common clinical use of 5-FU in the treatment of colon cancer, we investigated the effect of reconstitution of wild-type TGFBR2 on the sensitivity of colon cancer to 5-FU. Methods: V-410, a MMR proficient, mutant TGFBR2 (Arg528His) colon cancer cell line; V364, another MMR proficient cell line with absent TGFBR2 expression; and HCT116, a MMR deficient, mutant TGFBR2 cell line (BAT-RII mutation), were stably reconstituted with TGFBR2, treated with 5-FU, and then assessed in a colony forming assay. Activation of specific signaling pathways was also determined. Results: Reconstitution of TGFBR2 significantly sensitized both cell lines to 5-FU. Compared to the control cell lines, V-410-RII exhibited a 21-fold reduction in clonal surviving fraction with 5 μM 5-FU and HCT116-RII demonstrated a 7-fold reduction in clonal surviving fraction with 3 μM 5-FU. We observed a 50 % reduction in proliferation as measured by thymidine incorporation in V364-RII after treatment with 5 μM 5-FU. We next found that 5-FU treatment resulted in a TGFBR2 dependent activation of AP-1 signaling, but not of Smad signaling. No induction of AP-1 or Smad signaling was observed in the control cell line V364 RII D522N. Conclusions: Thus, reconstitution of wild-type TGFBR2 in colon cancer enhances 5-FU’s effects and may do so through an AP-1 dependent mechanism. Further studies are needed to determine whether AP-1 activation is required for the TGFBR2 mediated effects on 5-FU responsiveness.
Abstract 520: Overexpression of a Non-muscle RBFOX2 Splice Isoform Induce Cardiac Arrhythmias in Myotonic Dystrophy
Authors: CHAITALI MISRA, SUSHANT BANGRU, DARREN J PARKER, SARA KOENIG, ELLEN LUBBERS, JAMILA HEDHLI, THOMAS A COOPER, WAWRZYNIEC L DOBRUCKI, PETER MOHLER, AUINASH KALSOTRA
Journal: Circulation Research (2018)

Myotonic dystrophy type 1 (DM1) is a dominantly inherited neuromuscular disease caused by a CTG repeat expansion in 3’-UTR of DMPK gene. DM1 affects multiple tissues, but cardiac dysfunctions are the second leading cause of death which often include conduction defects and arrhythmias. The best characterized pathogenic mechanism of DM1 is toxic gain-of-function of expanded CUG repeat (CUG exp ) RNA that accumulates to form ribonuclear foci causing sequestration of MBNL and overexpression of CELF1 family of splicing factors. However, loss of MBNL or gain of CELF1 activity does not explain the cardiac phenotypes observed in DM1. Here we report that steady-state protein levels of RBFOX2, a critical splicing regulator, are drastically upregulated in DM1 heart tissue. This is accompanied by aberrant skipping of a muscle-specific 43bp exon in RBFOX2 transcript, resulting in selective up-regulation of the non-muscle RBFOX2 splice isoform in adult cardiomyocytes. We demonstrate that expression of CUG exp RNA in DM1 affects RBFOX2 in two distinct ways: reduced expression of a subset of microRNAs causes de-repression of RBFOX2 protein production; and CELF1 overexpression promotes skipping of the muscle-specific exon of RBFOX2 . Remarkably, tet -inducible overexpression of the non-muscle RBFOX2 isoform, or CRISPR/ Cas9 mediated deletion of the muscle-specific RBFOX2 exon in the mouse heart results in prolonged PR and QRS intervals, slower conduction velocity and spontaneous cardiac arrhythmias that mirror human DM1 pathology. Integration of RBFOX2-CLIP with RNA-seq data from cardiomyocytes of mice expressing the non-muscle RBFOX2 isoform identified a core network of mRNA splicing defects in genes encoding sodium, potassium, and calcium ion channels and key excitation-contraction coupling proteins that are similarly misspliced in hearts of DM1 patients. Thus, we have uncovered a central role for RBFOX2 isoform switching in DM1 cardiac pathogenesis and identified the molecular mechanisms that may alter electrophysiological properties and thereby induce cardiac arrhythmias in the DM1 heart.
STENT EDGE LANDING ZONE MORPHOLOGY BY OPTICAL COHERENCE TOMOGRAPHY AS A PREDICTOR OF STENT EDGE NEOINTIMAL HYPERPLASIA
Authors: Sofia Karlsson, Mitsuaki Matsumura, Stephen Lee, Chor Cheung Tam, Yangbo Liu, Shun Ling Kong, Gary Mintz, Akiko Maehara
Journal: Journal of the American College of Cardiology (2019)
NON VITAMIN K ORAL ANTICOAGULANTS ARE NOT ASSOCIATED WITH INCREASED RISK OF PERIOPERATIVE BLEEDING IN PATIENTS UNDERGOING CARDIAC SURGERY
Authors: Nathan Waldron, Peter Shrader, Jerrold Levy, Larry Allen, Paul Chan, Michael Ezekowitz, Gregg Fonarow, James Freeman, Bernard Gersh, Elaine Hylek, Peter Kowey, Kenneth Mahaffey, Gerald Naccarelli, James Reiffel, Daniel Singer, Benjamin Steinberg, Eric Peterson, Jonathan Piccini
Journal: Journal of the American College of Cardiology (2019)
HIV in the United States
Authors: Ingrid Katz, Ashish K. Jha
Journal: JAMA (2019)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
<i>CHEK2</i> Alleles Predispose to Renal Cancer in Poland
Authors: Elzbieta Zlowocka-Perlowska, Steven A. Narod, Cezary Cybulski
Journal: JAMA Oncology (2019)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal