tbuckley/cabot-search huggingface dataset:
Detection of Pediatric Pulmonary Arterial Hypertension by School Electrocardiography Mass Screening
Authors: Hirofumi Sawada, Yoshihide Mitani, Tomotaka Nakayama, Hiroyuki Fukushima, Shigetoyo Kogaki, Takehiro Igarashi, Fukiko Ichida, Yasuo Ono, Toshio Nakanishi, Shozaburo Doi, Shiro Ishikawa, Masaki Matsushima, Osamu Yamada, Tsutomu Saji
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: To detect pulmonary arterial hypertension (PAH) at any early stage is a promising approach to optimize the outcome.Objectives: To investigate the impact of school ECG-based screening on detecting idiopathic or heritable (I/H)-PAH in the general pediatric population.Methods: This was a nationwide survey of patients with I/H-PAH newly diagnosed at 3 months to 18 years of age in Japan during 2005–2012.Measurements and Main Results: Eighty-seven eligible patients (age range, 1–16 yr) were recruited. Among 68 (78%) patients diagnosed at greater than or equal to 6 years of age (the age of the first ECG-based screening), 28 (41%) were detected by the ECG-based screening (screening group) and 40 (59%) were recognized by their symptoms (n = 37) or coincidental occasions (n = 3; nonscreening group). In the screening group, the proportion of patients in World Health Organization functional class I/II at diagnosis was higher (96% vs. 60%; P < 0.001), plasma brain natriuretic peptide level was lower (149 ± 290 vs. 398 ± 559 pg/ml; P = 0.045), and 6-minute-walk distance was longer (420 ± 109 vs. 327 ± 104 m; P < 0.001) than the nonscreening group, despite similar values in mean pulmonary artery pressure (58 ± 17 vs. 61 ± 17 mm Hg; P = 0.42) and pulmonary vascular resistance index (18 ± 8 vs. 21 ± 11 Wood units ⋅ m2; P = 0.24) between groups. The proportion of patients on intravenous epoprostenol at the final visit was lower in the screening group than the nonscreening group (14% vs. 50; P = 0.004).Conclusions: These findings suggest that the ECG-based screening detects a unique subpopulation of pediatric patients with I/H-PAH that is associated with already established pulmonary hypertension but without obvious right heart failure and warrants investigating the prognostic significance of this system.
Abstract 16236: Perceived Control Mediates Association Between Health Literacy and Self-Care Behavior in Heart Failure Patients
Authors: Miyuki Tsuchihashi-Makaya, Shiho Matsuoka, Hiroko Ishida, Masako Saka, Etsuko Nakatsugawa
Journal: Circulation (2017)

Introduction: Heart failure (HF) patients benefit from self-care (SC) behavior in preventing exacerbation of their condition. Health literacy (HL) is an important skill for maintaining such behavio...
Alcohol drinking patterns and liver cirrhosis risk: analysis of the prospective UK Million Women Study
Authors: Rachel F Simpson, Carol Hermon, Bette Liu, Jane Green, Gillian K Reeves, Valerie Beral, Sarah Floud
Journal: The Lancet Public Health (2018)

Alcohol is a known cause of cirrhosis, but it is unclear if the associated risk varies by whether alcohol is drunk with meals, or by the frequency or type of alcohol consumed. Here we aim to investigate the associations between alcohol consumption with meals, daily frequency of consumption, and liver cirrhosis.
AB0062 Reciprocal interaction between macrophage migration inhibitory factor and interleukin-8 in gout
Authors: H.-R. Kim, S.-H. Lee, K.-A. Lee, K.-W. Kim
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Macrophage migration inhibitory factor is a proinflammatory, chemotactic, and tissue destructive cytokine. <h3>Objectives</h3> This study determined monosodium urate crystal-induced macrophage migration inhibitory factor production and its interaction with interleukin-8 in gout. <h3>Methods</h3> Peripheral blood, synovial fluid, and clinical data were obtained from 98 patients with gout. Synovial fluid and serum concentrations of macrophage migration inhibitory factor and interleukin-8 were measured. Synovial fluid monocytes and neutrophils were cultured with monosodium urate crystals and the cytokine production was determined. The signalling pathways involved were determined using signal inhibitors. The interaction between macrophage migration inhibitory factor and interleukin-8 was investigated. <h3>Results</h3> Synovial fluid macrophage migration inhibitory factor was higher in acute gout and that in serum was higher in patients with intercritical gout compared with controls. Synovial fluid macrophage migration inhibitory factor was positively correlated with synovial fluid leukocyte and neutrophil counts and interleukin-8. The expression of macrophage migration inhibitory factor was similar in synovial fluid neutrophils and monocytes, while interleukin-8 was higher in monocytes. Monosodium urate crystals induced macrophage migration inhibitory factor production in monocytes and interleukin-8 production in neutrophils. This effect was decreased by inhibiting Fc-gamma receptor 1 and toll-like receptor 4. Interleukin-8 increased macrophage migration inhibitory factor production in monocytes while macrophage migration inhibitory factor increased interleukin-8 production in neutrophils. <h3>Conclusions</h3> Macrophage migration inhibitory factor and interleukin-8 are highly produced in acute gout. Monosodium urate crystals induced macrophage migration inhibitory factor production in monocytes and interleukin-8 production in neutrophils with a reciprocal interaction between the two cytokines. <h3>Acknowledgements</h3> This work was supported by Konkuk University Medical Centre Research Grant 2016. <h3>Disclosure of Interest</h3> None declared
Association of immune-related adverse events and efficacy in Japanese patients with squamous cell carcinoma of the head and neck treated with nivolumab
Authors: T. Otsuka, K. Fujiishi, K. Matsumoto, T. Kimura, R. Koike, H. Cho, A. Hasegawa, M. Nishio, S. Otozai, T. Yoshii, T. Kudo, F. Fujisawa, N. Sugimoto, T. Yagi, F. Imamura, T. Fujii
Journal: Annals of Oncology (2018)
Does the Term <i>Intensive Care Unit</i> Promote Aggressive Treatment?
Authors: Brian L. Block
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Assessment of Myocardial Fibrosis Using Multimodality Imaging in Severe Aortic Stenosis
Authors: Sung-Ji Park, Sung Woo Cho, Sung Mok Kim, Joonghyun Ahn, Keumhee Carriere, Dong Seop Jeong, Sang-Chol Lee, Seung Woo Park, Yeon Hyeon Choe, Pyo Won Park, Jae K. Oh
Journal: JACC. Cardiovascular imaging (2018)
Targeted inhibition of ErbB heterodimers in the Calu3 lung cancer cell line
Authors: Parnetta Sutton, Philip Bonomi, Janet Plate
Journal: Cancer Research (2007)

2059  In cancer cells the ErbB/epidermal growth factor family of receptors (EGFR) which bind EGF and other ligands serve as effective targets for therapy. Expression of more than one ErbB family member, ErbB-1, ErbB-2, ErbB-3 or ErbB-4, leads to the formation of heterodimers or homodimers which have differential binding affinities and activation thresholds. Activating mutations in EGFR/ErbB-1 result in constitutive activation and perpetual growth of cells. In non-small cell lung cancer (nsclc) activating mutations in the kinase domain result in more effective responses to therapy targeted to EGFR. To gain a better understanding of the mechanisms of activation through ErbB family members in lung cancer, we undertook a study of ErbB signaling in non-small cell lung cancer cell lines where EGFR pathways were constitutively activated. In one line, calu3, EGFR was constitutively phosphorylated and culture with the EGFR specific inhibitor, AG1478 under usual conditions, failed to inhibit phosphorylation detected by anti-EGFR phospho-tyr992, while anti-EGFR phospho-tyr845 activity was only somewhat decreased. Further, culture with the neutralizing anti-EGFR monoclonal antibody, clone LA1, failed to inhibit constitutive tyr 992 and 845 phosphorylation. Control experiments with other nsclc cell lines demonstrated effective inhibition of EGF stimulated EGFR phosphorylation with either AG1478 or LA1 at both tyr 992 and 845. Thus, constitutive activation of EGFR in calu3 resulted in responses distinct from those observed in control cells following EGF stimulation. Constitutive activation was not due to activating mutations in the EGFR kinase domain as PCR analyses of ErbB-1 exons19 and 21 demonstrated normal sequences. The potential causes of constitutive activation were further investigated by Western blot analyses which revealed that ErbB-2 and ErbB-3 were coexpressed in the calu3 cell line. Immunoprecipitation experiments confirmed ErbB-2 and ErbB-3 co-expression. Western blots of the immunoprecipitates revealed that ErbB-3 served as the substrate for phosphorylation. Downstream signals that might also be activated as a result of constitutive activation of ErbB-3 were addressed by examining Akt, Erk1,2 and PKCδ phosphorylation. Western blots revealed that both Akt and Erk1,2 were constitutively activated as evidenced by Akt (ser473) and Erk1,2 p44/42 (thr202/tyr204) phosphorylation. Phosphorylation of Akt and PKCδ were totally blocked by inhibition with AG1478 while Erk1,2 phosphorylation was substantially decreased, but still evident. In control experiments, the Erk1,2 specific inhibitor U0126 totally inhibited phosphorylation of Erk1,2. These data reveal a complexity of constitutive activation that merits further investigation. It is our goal that the delineation of the mechanisms of constitutive EGFR/ErbB-3 activation may reveal additional sites that could be used for targeted therapy.
Promotion of Calcium/Calmodulin‐Dependent Protein Kinase 4 by GLUT1‐Dependent Glycolysis in Systemic Lupus Erythematosus
Authors: Tomohiro Koga, Tomohito Sato, Kaori Furukawa, Shimpei Morimoto, Yushiro Endo, Masataka Umeda, Remi Sumiyoshi, Shoichi Fukui, Shin‐ya Kawashiri, Naoki Iwamoto, Kunihiro Ichinose, Mami Tamai, Tomoki Origuchi, Hideki Nakamura, Atsushi Kawakami
Journal: Arthritis & Rheumatology (2018)

To clarify the significance of immunometabolism in systemic lupus erythematosus (SLE), and to determine the effect of calcium/calmodulin-dependent protein kinase 4 (CaMK4) on T cell metabolism.Metabolomic profiling was performed using capillary electrophoresis mass spectrometry in naive T cells from MRL/lpr mice treated with anti-CD3/CD28 antibodies in the absence or presence of a CaMK4 inhibitor (KN-93). The expression of GLUT1 and CaMK4 in CD4+ T cells from healthy controls (n = 16), patients with inactive SLE (n = 13), and patients with active SLE (n = 14) was examined by flow cytometry and quantitative polymerase chain reaction. In vitro experiments were performed to determine the effect of KN-93 on the expression of GLUT1 during Th17 cell differentiation in T cells from patients with SLE.CaMK4 inhibition significantly decreased the levels of glycolytic intermediates such as glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, pyruvate, and lactate (P < 0.05), whereas it did not affect the levels of the pentose phosphate pathway intermediates such as 6-phospho-d-gluconate, ribulose-5-phosphate, ribose-5-phosphate, and phosphoribosyl pyrophosphate. The expression levels of GLUT1 and CaMK4 in effector memory CD4+ T cells were significantly higher in patients with active SLE compared to healthy controls (P < 0.01 and P < 0.05, respectively) and patients with inactive SLE (P < 0.05 and P < 0.01, respectively). A functional analysis revealed that CaMK4 inhibition decreased the expression of GLUT1 during Th17 cell differentiation (P < 0.01), followed by a reduction of interleukin-17 (IL-17) production (P < 0.05).The results of the study indicate that the activity of CaMK4 could be responsible for glycolysis, which contributes to the production of IL-17, and CaMK4 may contribute to aberrant expression of GLUT1 in T cells from patients with active SLE.
SELECT: A Phase II Trial of Adjuvant Erlotinib in Patients With Resected Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer
Authors: Nathan A. Pennell, Joel W. Neal, Jamie E. Chaft, Christopher G. Azzoli, Pasi A. Jänne, Ramaswamy Govindan, Tracey L. Evans, Daniel B. Costa, Heather A. Wakelee, Rebecca S. Heist, Marc A. Shapiro, Alona Muzikansky, Sudish Murthy, Michael Lanuti, Valerie W. Rusch, Mark G. Kris, Lecia V. Sequist
Journal: Journal of Clinical Oncology (2018)

Purpose Given the pivotal role of epidermal growth factor receptor (EGFR) inhibitors in advanced EGFR-mutant non–small-cell lung cancer (NSCLC), we tested adjuvant erlotinib in patients with EGFR-mutant early-stage NSCLC. Materials and Methods In this open-label phase II trial, patients with resected stage IA to IIIA (7 th edition of the American Joint Committee on Cancer staging system) EGFR-mutant NSCLC were treated with erlotinib 150 mg per day for 2 years after standard adjuvant chemotherapy with or without radiotherapy. The study was designed for 100 patients and powered to demonstrate a primary end point of 2-year disease-free survival (DFS) greater than 85%, improving on historic data of 76%. Results Patients (N = 100) were enrolled at seven sites from January 2008 to May 2012; 13% had stage IA disease, 32% had stage IB disease, 11% had stage IIA disease, 16% had stage IIB disease, and 28% had stage IIIA disease. Toxicities were typical of erlotinib; there were no grade 4 or 5 adverse events. Forty percent of patients required erlotinib dose reduction to 100 mg per day and 16% to 50 mg per day. The intended 2-year course was achieved in 69% of patients. The median follow-up was 5.2 years, and 2-year DFS was 88% (96% stage I, 78% stage II, 91% stage III). Median DFS and overall survival have not been reached; 5-year DFS was 56% (95% CI, 45% to 66%), 5-year overall survival was 86% (95% CI, 77% to 92%). Disease recurred in 40 patients, with only four recurrences during erlotinib treatment. The median time to recurrence was 25 months after stopping erlotinib. Of patients with recurrence who underwent rebiopsy (n = 24; 60%), only one had T790M mutation detected. The majority of patients with recurrence were retreated with erlotinib (n = 26; 65%) for a median duration of 13 months. Conclusion Patients with EGFR-mutant NSCLC treated with adjuvant erlotinib had an improved 2-year DFS compared with historic genotype-matched controls. Recurrences were rare for patients receiving adjuvant erlotinib, and patients rechallenged with erlotinib after recurrence experienced durable benefit.
THU0078 Berberine ameliorates bone erosions in collagen-induced arthritis rat models via suppressing the expression of il-17a
Authors: J. Yue, J. Xu, H. Li, J. Wang, N. Zheng, H. Yao, L.-S. Tam, L. Qin
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic progressive disease characterised by synovial inflammation, autoantibody production, cartilage and bone destruction. Bone erosions are a key feature of RA reflecting both disease severity and disease progression. An imbalance between Th17 and regulatory T cells (Treg cells) has been extensively recognised in both patients and model animals of RA. Oral administration of berberine, an isoquinoline alkaloid, has been showed to ameliorate various symptoms of autoimmune diseases including RA. <h3>Objectives</h3> To verify whether berberine may prevent bone erosions during RA progression and to explore the potential mechanisms in Collagen-induced arthritis (CIA) rat model. <h3>Methods</h3> The severity of arthritis was expressed as mean arthritic index on a 0–4 scale according to the following criteria: 0=no oedema or swelling; 1=slight oedema and erythema limited to the foot and/or ankle; 2=slight oedema and erythema from the ankle to the tarsal bone; 3=moderate oedema and erythema from the ankle to the tarsal bone; and 4=severe oedema and erythema from the ankle to the entire leg. Each limb was graded, and thus the maximum possible score was 16 for each animal. The threshold score of rats with established CIA is 2. The CIA rats were divided into 3 groups: placebo group (n=4), low dose berberine group (50 mg/kg/day, n=4) and high dose berberine group (200 mg/kg/day, n=4). Placebo and berberine were intragastrically administered to all rats for 4 and 8 weeks after the CIA models were established. TNF-α, IL-1β, IL-6, IL-17A, and IgG in the serum were measured by ELISA kits (purchased from Abcam). The hind paws of rats were scanned by micro CT (Scanco, Switzerland). <h3>Results</h3> The thickness of the swollen hind paws was reduced in the high dose berberine group (200 mg/kg/day) compared with the placebo group (Fig A). No significant differences were observed in the levels of TNF-α, IL-1β, and IL-6 between the three groups. However, the levels of IL-17A and IgG were significantly decreased in the high dose berberine group when compared with the placebo group (Fig A). Micro CT data revealed that berberine could significantly improve the microstructure of CIA rats including the bone volume ratio (BV/TV), areal bone mineral density (aBMD) and trabecular separation (Tb Sp) (Fig B and C). Development of bone erosion had also been partially prevented. <b>Figure 1</b> A; B microstructure; C 3D reconstruction <h3>Conclusions</h3> Berberine attenuated the symptoms of CIA rats and may prevent bone erosion progression by suppressing IL-17A in CIA. Human studies are required to confirm whether it may serve as a potential treatment for RA in the future. <h3>Disclosure of Interest</h3> None declared
Abstract 17075: Inhibition of Adenosine A2B Receptor Ameliorates Renal Fibrosis by Regulating Macrophage Infiltration and Polarization
Authors: Tingting Xie, Guoli Li, Hui Yang, Xuan Wang, Jiarong Li, Weiru Zhang
Journal: Circulation (2017)

Introduction: It is widely accepted that macrophage recruitment and polarization play a prominent role in the development of renal fibrosis. Our previous studies have demonstrated that persistently...
Transmembrane Protease, Serine 6 (TMPRSS6) Antisense Oligonucleotide (IONIS-TMPRSS6-LRX) Reduces Plasma Iron Levels of Healthy Volunteers in a Phase 1 Clinical Study
Authors: Michael McCaleb, Jason Lickliter, Andrew Dibble, Eugene Schneider, Mariam Aghajan, Shuling Guo, Steve Hughes, Richard S Geary, Brett P. Monia
Journal: Blood (2018)
Abstract 17603: Inhaled Nitric Oxide Improves Cerebral Mitochondrial Function in a Blinded, Randomized Controlled Pediatric Swine Asphyxial Cardiac Arrest Trial
Authors: Constantine D Mavroudis, Michael Karlsson, Tiffany Ko, Ryan Morgan, Ross Plyler, Melissa Byro, Kobina Mensah-Brown, Timothy Boorady, Andrew Lautz, Javier I Gentile, Vinay M Nadkarni, Robert A Berg, Robert A Sutton, Daniel J Licht, Todd J Kilbaugh
Journal: Circulation (2017)

Introduction: Neurologic injury following pediatric cardiac arrest (CA) remains common. Inhaled nitric oxide (iNO) may mitigate cerebral mitochondrial dysfunction, a critical convergence point for ...
Autophagy defect increases chromosome instability under metabolic stress
Authors: Haiyan Zhang, Yong Zhang, Robin Mathew, Brian Beaudoin, Robert Taylor, Noboru Mizushima, Eileen White, Shengkan Jin
Journal: Cancer Research (2007)

4916  Autophagy, a process responsible for bulk protein and organelle degradation is implicated in tumor suppression. In humans, monoallelic deletion of beclin 1 is prevalent in tumors, and mice with targeted allelic deletion of beclin 1 have increased cancer rates. However, exactly how autophagy suppresses cancer development is not clear. On the other hand, a fundamental and conserved function of autophagy is alleviating metabolic stress. Autophagy is found to be activated at the center of a tumor to mitigate the metabolic stress caused by inefficient oxygen and nutrient diffusion, and support cell survival. It is also not clear how the loss of a survival mechanism paradoxically increases tumorigenicity. Here we show that autophagy deficiency promotes chromosome instability by increasing abnormal centrosome duplication and mitosis under metabolic stress. Time-lapse microscopy showed that under amino acid deprivation the T-antigen immortalized mouse embryonic fibroblasts (iMEFs) derived from mice with a targeted deletion of an essential autophagy gene, atg5, exhibited an increased frequency of aberrant mitosis that included tripolar division and endomitosis as compared to their wild type counterparts. Metabolic stress significantly increased the percentage of the atg5-/- cells containing 3 or more centrosomes, while it had little effect on the atg5+/+ cells. Similarly, knocking down the expression of another essential autophagy gene beclin 1 with siRNA in the atg5+/+ iMEFs led to a similar phenotype as observed in the atg5-/- cells. Furthermore, the atg5-/- cells exhibited higher chromosome instability than the atg5+/+ cells under metabolic stress as determined by the rate of gene amplification. Together, our results suggest that autophagy may suppress tumor development through reducing chromosome instability by mitigating metabolic stress, thereby preventing tumor progression.
Abstract 16134: Different Roles of Myocardial ROCK1 and ROCK2 in Response to Chronic Pressure-Overload in Mice
Authors: Shinichiro Sunamura, Kimio Satoh, Toru Shimizu, Kota Suzuki, Shohei Ikeda, Shun Kudo, Junichi Omura, Nobuhiro Kikuchi, Taijyu Satoh, Ryo Kurosawa, Masamichi Nogi, Tomohiro Ohtsuki, Hiroaki Shimokawa
Journal: Circulation (2017)

Background: Rho-kinase plays a crucial role in the development of cardiac hypertrophy and failure. However, possible different roles of myocardial Rho-kinase isoforms, ROCK1 and ROCK2, remain to be...
Efficacy and safety of single-agent arsenic trioxide (ATO) as an induction regimen in the treatment of newly diagnosed acute promyelocytic leukemia (APL): A prospective single arm phase II study from South India
Authors: P.V. Simha, D. Lokanatha, K. Govind Babu, L.A. Jacob, M.C. Suresh Babu, K.N. Lokesh, A.H. Rudresha, L.K. Rajeev, S.C. Smitha, G.V. Giri
Journal: Annals of Oncology (2018)