tbuckley/cabot-search huggingface dataset:
Bowman’s capsule provides a protective niche for podocytes from cytotoxic CD8+ T cells
Authors: Anqun Chen, Kyung Lee, Vivette D. D’Agati, Chengguo Wei, Jia Fu, Tian-Jun Guan, John Cijiang He, Detlef Schlondorff, Judith Agudo
Journal: Journal of Clinical Investigation (2018)

T cells play a key role in immune-mediated glomerulonephritis, but how cytotoxic T cells interact with podocytes remains unclear. To address this, we injected EGFP-specific CD8+ T cells from just EGFP death inducing (Jedi) mice into transgenic mice with podocyte-specific expression of EGFP. In healthy mice, Jedi T cells could not access EGFP+ podocytes. Conversely, when we induced nephrotoxic serum nephritis (NTSN) and injected Jedi T cells, EGFP+ podocyte transgenic mice showed enhanced proteinuria and higher blood urea levels. Morphometric analysis showed greater loss of EGFP+ podocytes, which was associated with severe crescentic and necrotizing glomerulonephritis. Notably, only glomeruli with disrupted Bowman's capsule displayed massive CD8+ T cell infiltrates that were in direct contact with EGFP+ podocytes, causing their apoptosis. Thus, under control conditions with intact Bowman's capsule, podocytes are not accessible to CD8+ T cells. However, breaches in Bowman's capsule, as also noted in human crescentic glomerulonephritis, allow access of CD8+ T cells to the glomerular tuft and podocytes, resulting in their destruction. Through these mechanisms, a potentially reversible glomerulonephritis undergoes an augmentation process to a rapidly progressive glomerulonephritis, leading to end-stage kidney disease. Translating these mechanistic insights to human crescentic nephritis should direct future therapeutic interventions at blocking CD8+ T cells, especially in progressive stages of rapidly progressive glomerulonephritis.
Antivirulence Therapy: Broad-Spectrum Neutralization of Pore-Forming Toxins with Human Erythrocyte Membrane-Coated Nanosponges (Adv. Healthcare Mater. 13/2018)
Authors: Yijie Chen, Mengchun Chen, Yue Zhang, Joo Hee Lee, Tamara Escajadillo, Hua Gong, Ronnie H. Fang, Weiwei Gao, Victor Nizet, Liangfang Zhang
Journal: Advanced Healthcare Materials (2018)

In article 1701366 by Liangfang Zhang and co-workers, human red blood cell (RBC) nanosponges are designed and demonstrated to concurrently absorb various types of different virulence factors including those from methicillin-resistant Staphylococcus aureus, Listeria monocytogenes, and Group A Streptococcus. Toxins absorbed by the nanosponges are no longer able to damage healthy RBCs or other normal human cells both in vitro and in vivo.
CONTRAST-ENHANCED ENDOSCOPIC ULTRASOUND VERSUS MULTIDETECTOR COMPUTED TOMOGRAPHY TO DIFFERENTIATE PANCREATIC CANCER FROM CHRONIC PANCREATITIS
Authors: F Harmsen, D Domagk, CF Dietrich, M Hocke
Journal: Endoscopy (2018)

To compare multidetector computed tomography and contrast-enhanced endoscopic ultrasound in their capacity to differentiate chronic pancreatitis from pancreatic carcinoma.
P53 IMMUNOEXPRESSION IN HIGH DEGREE DYSPLASIA COLON ADENOMAS FROM CHOLECYSTECTOMIZED CUBAN PATIENTS AND WITH CHOLELITHIASIS
Authors: FN Piñol Jiménez, L González Fabian, M Morera
Journal: Endoscopy (2018)

The progression of adenoma to adenocarcinoma is a result of inherited or acquired genetic factors present in intestinal cells.
Hallazgos no neoplásicos en participantes del programa de cribado de cáncer colorrectal en Burgos
Authors: G Hontoria Bautista, MA Jiménez Moreno, R Pereda García, J Sanz Sánchez, B Bernad Cabredo, E Badia Aranda, B Sicilia Aladrén, S García Morán, JL Martin Lorente, F Sáez-Royuela Gonzalo
Journal: Endoscopy (2017)

El programa de cribado del cáncer colorrectal (CCR) ha demostrado detectar CCR en estadíos precoces, permitiendo un tratamiento más efectivo. Sin embargo, otros hallazgos no neoplásicos (HNN) se detectan en las colonoscopias tras un test de sangre oculta en heces (SOH) positivo.
Julian Tudor Hart: visionary general practitioner who introduced the concept of the “inverse care law”
Authors: Penny Warren
Journal: BMJ (2018)

Credit: Ben Tudor Hart

In 1971 a GP from a Welsh mining village submitted a paper to the Lancet . More than 45 years later doctors, researchers, and politicians still quote Julian Tudor Hart’s “inverse care law.”1

It states: “The availability of good medical care tends to vary inversely with the need for it in the population served. This inverse care law operates more completely where medical care is most exposed to market forces, and less so where such exposure is reduced.”

It’s fitting that Tudor Hart, a fierce critic of market forces in medicine, should die aged 91 on the 70th anniversary of the NHS, which he defended so passionately.

Tudor Hart was born in London in 1927 into a communist medical family. He once described home as something of a “transit camp for antifascist refugees” and said that his father gave him works of Marx to read at school.

In 1940, aged 13, he and his sisters took refuge in Canada from the second world war with their grandfather, the artist …
Abstract 4558: Dynamic Right Ventricular Function Assessment by Real-Time 3D Echography in Combination with Semiautomatic Endocardial Detection in Adults with Corrected Tetralogy of Fallot: Comparison with Magnetic Resonance Imaging
Authors: Xavier Iriart, Michel Montaudon, Stephane Lafitte, Hanane Bougteb, Francois Laurent, Patricia Reant, Thomas Balbach, Jean-Benoit Thambo
Journal: Circulation (2008)
Diagnóstico de enfermedad de Crohn de intestino delgado en el seguimiento de pacientes con cápsula endoscópica inicial negativa
Authors: A Ortega Sabater, J Egea Valenzuela, P Tomás Pujante, E Iglesias Jorquera, A Sánchez Torres, G Antón Ródenas, M Muñoz Tornero, T Fernández Llamas, AV García Marín, F Alberca
Journal: Endoscopy (2017)

La cápsula endoscópica (CE) es la técnica de elección en pacientes con sospecha de enfermedad de Crohn (EC) de intestino delgado (ID). En este escenario tiene un excelente valor predictivo negativo, por encima del 90% en la mayoría de series publicadas. Por otra parte, la escala de Lewis, validada para establecer la severidad de la afectación inflamatoria, también ha demostrado ser útil para delimitar la significación de las lesiones inflamatorias, suponiendo una puntuación por debajo de 135 un estudio negativo o con lesiones no significativas para establecer un diagnóstico endoscopio de EC.
Too small, too soon
Authors: Jonathan Starke
Journal: JAMA (2018)

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
NOTCH3 contributes to rhinovirus-induced goblet cell hyperplasia in COPD airway epithelial cells
Authors: Yaxun Jing, Joao Antonio Gimenes, Rahul Mishra, Duc Pham, Adam T Comstock, Daohai Yu, Umadevi Sajjan
Journal: Thorax (2018)

Rationale Goblet cell hyperplasia (GCH) is one of the cardinal features of chronic obstructive pulmonary disease (COPD) and contributes to airways obstruction. Rhinovirus (RV), which causes acute exacerbations in patients with COPD, also causes prolonged airways obstruction. Previously, we showed that RV enhances mucin gene expression and increases goblet cell number in a COPD mouse model. This study examines whether RV causes sustained GCH in relevant models of COPD. Methods Mucociliary-differentiated COPD and normal airway epithelial cell cultures and mice with normal or COPD phenotype were infected with RV or sham and examined for GCH by immunofluorescence and/or mucin gene expression. In some experiments, RV-infected COPD cells and mice with COPD phenotype were treated with γ-secretase inhibitor or interleukin-13 neutralising antibody and assessed for GCH. To determine the contribution of NOTCH1/3 in RV-induced GCH, COPD cells transduced with NOTCH1/3 shRNA were used. Results RV-infected COPD, but not normal cell cultures, showed sustained GCH and increased mucin genes expression. Microarray analysis indicated increased expression of NOTCH1, NOTCH3 and HEY1 only in RV-infected COPD cells. Blocking NOTCH3, but not NOTCH1, attenuated RV-induced GCH in vitro. Inhibition of NOTCH signalling by γ-secretase inhibitor, but not neutralising antibody to IL-13, abrogated RV-induced GCH and mucin gene expression. Conclusions RV induces sustained GCH via NOTCH3 particularly in COPD cells or mice with COPD phenotype. This may be one of the mechanisms that may contribute to RV-induced prolonged airways obstruction in COPD.
Abstract 34: Acetylation of GATA 4 Enhanced Direct Cardiac Reprogramming of Induced Cardiomyocytes
Authors: Vivek P Singh, Megumi Mathison, Jaya P Pinnamaneni, Deepthi Sanagasetti, Narasimhaswamy S Belaguli, Sonal Somvanshi, Jacqueline K Olive, Jianchang Yang, Todd K Rosengart
Journal: Circulation Research (2017)

Objective: Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) by forced expression of cardiomyogenic factors, GMT (GATA4, Mef2c and Tbx5), has recently been demonstrated, suggesting a promising statregy for cardiac regeneration. However, the efficiency of direct reprogramming is usually relatively low and requires extensive epigenetic redesigning, although the underlying mechanism are largely unknown. Methods: In a recent study, we created a novel mutation in rat GATA 4 by replacing lysine residue with glutamine at position 299 i.e. (K299Q), to mimic constitutive acetylation and examined whether constitutive acetylation of GATA4, when compared with wild type GATA4, further enhance GMT-mediated direct reprogramming efficiency of induced cardiomyocytes in vitro and accordingly ventricular function after myocardial infarction in rat, in vivo . Results: We found that acetylated GATA 4 (K299Q), in the presence of Mef2c and Tbx5 upregulated cardiac-specific markers, suppressed fibroblast genes, in rat cardiac fibroblasts (RCFs) more efficiently when compared with Mef2c, Tbx5 plus wild type GATA4. FACS analyses revealed that G(K299Q) MT induced significantly more cardiomyocyte marker cardiac troponin T (cTnT) expression compared with GMT alone. Mechanistic studies demonstrated that the K299Q substitution, resulting in enriched p300 occupancy at the GATA 4 promoter, induced acetylation of Histine 3, decreased HDAC expression. In addition, substitution augmented the increase in an acetylated form of GATA-4 and its DNA binding and transcriptional activity, compared with wildtype GATA 4. In agreement with upregulated cTNT gene expression in vitro , echocardiographic analysis demonstrate that the acetylated G(K299Q) MT vectors have improved effect in enhancing ventricular function than GMT vectors from postinfarct baselines as compared to negative control [G(K299Q) MT, 15.6% ± 2.7%; G(WT)MT, 12.8% ± 1.7%; GFP, -2.3% ± 1.1%]. Conclusions: Collectivily, these data indicate that acetylated GATA4 (K299Q) significantly increases reprogramming efficiency of induced cardiomyocytes (iCMs), in vitro and in vivo, and provide new insight into the molecular mechanism underlying cardiac regeneration.
Abstract 15814: Risk of Arrhythmia Recurrence in Patients With Typical Atrial Flutter With Proven Pulmonary Vein Antrum Isolation or Persistent Cavo-tricuspid Isthmus Block
Authors: Sanghamitra Mohanty, Luigi Di Biase, Chintan Trivedi, Carola Gianni, John David Burkhardt, Javier E Sanchez, Amin Al-Ahmad, Rodney Horton, Gemma Pellargonio, Giovanni Forleo, Sakis Themistoclakis, Michela Casella, Antonio Dello Russo, Claudio Tondo, Andrea Natale
Journal: Circulation (2016)

Introduction:  Cavo-tricuspid isthmus isolation (CTI) effectively targets typical atrial flutter (AFL) with a reported success rate of >85%. However, the incidence of new-onset atrial fibrillation (AF) following CTI remains high at around 50%.   Objective:  This study examined the risk of AF and AFL in patients undergoing pulmonary vein antrum isolation (PVAI) or CTI for typical AFL only.   Methods:  Forty-seven consecutive patients that have received either CTI only (group 1: n=21, 63.7±7.1 year, 75% male) or PVAI (group 2: n=26, 64.5±5.7 year, 73% male) for lone typical AFL were enrolled in this prospective analysis. Three months after the index ablation, a second procedure was performed to confirm persistent isolation of PVs and CT block. All patients were followed up for recurrence for 19±7 months after the second procedure with event-recorders and 7-day Holter monitoring.   Results:  Baseline characteristics were similar between the two groups. During the second procedure, persistence of isolation was confirmed in all patients except 1 from group 1 (95%) and in 22 of 26 (84.6%) patients in group 2. Only those subjects that had persistent CT block and PV-isolation (group 1: 20 and group 2: 22) were followed up for this analysis. At the end of 19±7 months, 1 patient from group 1 (5%) and 2 from group 2 (9%) had recurrence of typical AFL (p=0.99) whereas new-onset AF was detected in 10 (50%) and 3 (13.6%) patients from group 1 and 2 respectively (p=0.01).   Conclusion:  Our findings suggest that pulmonary vein triggers play an important role in atrial flutter and PVAI successfully prevents the recurrence of both AF and AFL compared to CTI only in patients presenting with lone typical atrial flutter.
Racial Differences in Long-Term Outcomes Among Older Survivors of In-Hospital Cardiac Arrest
Authors: Lena M. Chen, Brahmajee K. Nallamothu, John A. Spertus, Yuanyuan Tang, Paul S. Chan
Journal: Circulation (2018)

Background: Black patients have worse in-hospital survival than white patients after in-hospital cardiac arrest (IHCA), but less is known about long-term outcomes. We sought to assess among IHCA survivors whether there are additional racial differences in survival after hospital discharge and to explore potential reasons for differences. Methods: This was alongitudinal study of patients ≥65 years of age who had an IHCA and survived until hospital discharge between 2000 and 2011 from the national Get With The Guidelines–Resuscitation registry whose data could be linked to Medicare claims data. Sequential hierarchical modified Poisson regression models evaluated the proportion of racial differences explained by patient, hospital, and unmeasured factors. Our exposure was black or white race. Our outcome was survival at 1, 3, and 5 years. Results: Among 8764 patients who survived to discharge, 7652 (87.3%) were white and 1112 (12.7%) were black. Black patients with IHCA were younger, more frequently female, sicker with more comorbidities, less likely to have a shockable initial cardiac arrest rhythm, and less likely to be evaluated with coronary angiography after initial resuscitation. At discharge, black patients were also more likely to have at least moderate neurological disability and less likely to be discharged home. Compared with white patients and after adjustment only for hospital site, black patients had lower 1-year (43.6% versus 60.2%; relative risk [RR], 0.72), 3-year (31.6% versus 45.3%; RR, 0.71), and 5-year (23.5% versus 35.4%; RR, 0.67; all P &lt;0.001) survival. Adjustment for patient factors explained 29% of racial differences in 1-year survival (RR, 0.80; 95% confidence interval, 0.75–0.86), and further adjustment for hospital treatment factors explained an additional 17% of racial differences (RR, 0.85; 95% confidence interval, 0.80–0.92). Approximately half of the racial difference in 1-year survival remained unexplained, and the degree to which patient and hospital factors explained racial differences in 3-year and 5-year survival was similar. Conclusions: Black survivors of IHCA have lower long-term survival compared with white patients, and about half of this difference is not explained by patient factors or treatments after IHCA. Further investigation is warranted to better understand to what degree unmeasured but modifiable factors such as postdischarge care account for unexplained disparities.
Estudio comparativo de la eficacia y seguridad de la incisión única con bisturí de aguja (SINK) versus USE-ProCore en el diagnóstico de lesiones subepiteliales gástricas
Authors: A Montenegro Almeida, C Sánchez Montes, J Melo, O Sendino, C Rodríguez De Miguel, J Llach, À Ginès, G Fernández-Esparrach
Journal: Endoscopy (2017)

Los tumores subepiteliales (TSE) son lesiones localizadas en la pared del tubo digestivo debajo del epitelio. La ultrasonografía endoscópica (USE) con obtención de una muestra cito/histológica es la técnica de elección para evaluarlos, siendo su eficacia limitada. Se requieren nuevas técnicas para mejorar su rendimiento diagnóstico.
Molecular Imaging of Radiolabeled Bispecific T-Cell Engager 89Zr-AMG211 Targeting CEA-Positive Tumors
Authors: Stijn J.H. Waaijer, Frank J. Warnders, Sabine Stienen, Matthias Friedrich, Alexander Sternjak, H. Kam Cheung, Anton G.T. Terwisscha van Scheltinga, Carolien P. Schröder, Elisabeth G.E. de Vries, Marjolijn N. Lub-de Hooge
Journal: Clinical Cancer Research (2018)

Abstract Purpose: AMG 211, a bispecific T-cell engager (BiTE) antibody construct, targets carcinoembryonic antigen (CEA) and the CD3 epsilon subunit of the human T-cell receptor. AMG 211 was labeled with zirconium-89 (89Zr) or fluorescent dye to evaluate the tumor-targeting properties. Experimental Design: 89Zr-AMG211 was administered to mice bearing CEA-positive xenograft tumors of LS174T colorectal adenocarcinoma or BT474 breast cancer cells, as well as CEA-negative HL-60 promyelocytic leukemia xenografts. Biodistribution studies with 2- to 10-μg 89Zr-AMG211 supplemented with unlabeled AMG 211 up to 500-μg protein dose were performed. A BiTE that does not bind CEA, 89Zr-Mec14, served as a negative control. 89Zr-AMG211 integrity was determined in tumor lysates ex vivo. Intratumoral distribution was studied with IRDye800CW-AMG211. Moreover, 89Zr-AMG211 was manufactured according to Good Manufacturing Practice (GMP) guidelines for clinical trial NCT02760199. Results: 89Zr-AMG211 demonstrated dose-dependent tumor uptake at 6 hours. The highest tumor uptake was observed with a 2-μg dose, and the lowest tumor uptake was observed with a 500-μg dose. After 24 hours, higher uptake of 10-μg 89Zr-AMG211 occurred in CEA-positive xenografts, compared with CEA-negative xenografts. Although the blood half-life of 89Zr-AMG211 was approximately 1 hour, tumor retention persisted for at least 24 hours. 89Zr-Mec14 showed no tumor accumulation beyond background level. Ex vivo autoradiography revealed time-dependent disintegration of 89Zr-AMG211. 800CW-AMG211 was specifically localized in CEA-expressing viable tumor tissue. GMP-manufactured 89Zr-AMG211 fulfilled release specifications. Conclusions: 89Zr-AMG211 showed dose-dependent CEA-specific tumor targeting and localization in viable tumor tissue. Our data enabled its use to clinically evaluate AMG 211 in vivo behavior. Clin Cancer Res; 24(20); 4988–96. ©2018 AACR.
Epithelial activators of type 2 inflammation: Elevation of thymic stromal lymphopoietin, but not <scp>IL</scp>‐25 or <scp>IL</scp>‐33, in chronic rhinosinusitis with nasal polyps in Chicago, Illinois
Authors: Noriko Ogasawara, Aiko I. Klingler, Bruce K. Tan, Julie A. Poposki, Kathryn E. Hulse, Whitney W. Stevens, Anju T. Peters, Leslie C. Grammer, Kevin C. Welch, Stephanie S. Smith, David B. Conley, Robert C. Kern, Robert P. Schleimer, Atsushi Kato
Journal: Allergy (2018)

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ANALYSIS OF WIRE-GUIDED HEMOSTASIS INTRODUCER FOR PERCUTANEOUS THERAPY OF BILE DUCT STONES
Authors: M Hollenbach, J Feisthammel, J Mössner, A Hoffmeister
Journal: Endoscopy (2018)

Bile duct stones (BDS) are usually removed via ERCP or, if ERCP remains unsuccessful, PTCD. However, PTCD provides limited access to large BDS. We analyzed a modified approach of PTCD for percutaneous therapy of BDS.
European recommendations for the management of healthcare workers occupationally exposed to hepatitis B virus and hepatitis C virus
Authors: V Puro, G De Carli, S Cicalini, F Soldani, U Balslev, J Begovac, L Boaventura, M Campins Marti, M J Hernández Navarrete, R Kammerlander, C Larsen, F Lot, S Lunding, U Marcus, L Payne, A A Pereira, T Thomas, G Ippolito
Journal: Eurosurveillance (2005)

Exposure prevention is the primary strategy to reduce the risk of occupational bloodborne pathogen infections in healthcare workers (HCW). HCWs should be made aware of the medicolegal and clinical relevance of reporting an exposure, and have ready access to expert consultants to receive appropriate counselling, treatment and follow-up. Vaccination against hepatitis B virus (HBV), and demonstration of immunisation before employment are strongly recommended. HCWs with postvaccinal anti-HBs levels, 1-2 months after vaccine completion, &amp;gt;10 mIU/mL are considered as responders. Responders are protected against HBV infection: booster doses of vaccine or periodic antibody concentration testing are not recommended. Alternative strategies to overcome non-response should be adopted. Isolated anti-HBc positive HCWs should be tested for anti-HBc IgM and HBV-DNA: if negative, anti-HBs response to vaccination can distinguish between infection (anti-HBs &amp;gt;50 mUI/ml 30 days after 1st vaccination: anamnestic response) and false positive results(anti-HBs &amp;gt;10 mUI/ml 30 days after 3rd vaccination: primary response); true positive subjects have resistance to re-infection. and do not need vaccination The management of an occupational exposure to HBV differs according to the susceptibility of the exposed HCW and the serostatus of the source. When indicated, post-exposure prophylaxis with HBV vaccine, hepatitis B immunoglobulin or both must be started as soon as possible (within 1-7 days). In the absence of prophylaxis against hepatitis C virus (HCV) infection, follow-up management of HCV exposures depends on whether antiviral treatment during the acute phase is chosen. Test the HCW for HCV-Ab at baseline and after 6 months; up to 12 for HIV-HCV co-infected sources. If treatment is recommended, perform ALT (amino alanine transferase) activity at baseline and monthly for 4 months after exposure, and qualitative HCV-RNA when an increase is detected.
Abstract 13827: p66Shc, a Longevity Adaptor Protein, is Involved in ROS-Dependent Activation of VEGF Receptor 2 and AMP Kinase: Role in VEGF-Induced Energy Metabolism and Angiogenesis
Authors: Seok-Jo Kim, Norifumi Urao, Jin Oshikawa, Cristiana Caliceti, Eiji Furuta, Gin-Fu Chen, Ronald D McKinney, Tohru Fukai, Masuko Ushio-Fukai
Journal: Circulation (2011)

p66Shc is a master regulator of mitochondrial reactive oxygen species (ROS)(mtROS) production involved in aging and cardiovascular diseases.We demonstrated that ROS derived from NADPH oxidase (Nox)...