tbuckley/cabot-search huggingface dataset:
CircMET promotes tumor proliferation by enhancing CDKN2A mRNA decay and upregulating SMAD3
Authors: Lei Yang, Yi Chen, Ning Liu, Yanwen Lu, Wenliang Ma, Zhenhao Yang, Weidong Gan, Dongmei Li
Journal: Molecular Cancer (2022)

Functions of CircMET (hsa_circ_0082002) which is a circular RNA and derived from MET gene remain understood incompletely. In the present study, Xp11.2 translocation/NONO-TFE3 fusion renal cell carcinoma (NONO-TFE3 tRCC) with up-regulated CircMET was employed to investigate its mechanism in cancer progression and post-transcriptional regulation.FISH and real-time PCR were performed to explore the expression and localization circMET in NONO-TFE3 tRCC tissues and cells. The functions of circMET in tRCC were investigated by proliferation analysis, EdU staining, colony and sphere formation assay. The regulatory mechanisms among circMET, CDKN2A and SMAD3 were investigated by luciferase assay, RNA immunoprecipitation, RNA pulldown and targeted RNA demethylation system.The expression of circMET was upregulated by NONO-TFE3 fusion in NONO-TFE3 tRCC tissues and cells, and overexpression of circMET significantly promoted the growth of NONO-TFE3 tRCC. Mechanistic studies revealed that circMET was delivered to cytosol by YTHDC1 in N6-methyladenosine (m6A)-depend manner. CircMET enhances mRNA decay of CDKN2A by direct interaction and recruitment of YTHDF2. Meanwhile, circMET competitively absorbed miR-1197 and prevented those from SMAD3 mRNA.CircMET promotes the development of NONO-TFE3 tRCC, and the regulation to both CDKN2A and SMAD3 of circMET was revealed. CircMET has the potential to serve as a novel target for the molecular therapy of NONO-TFE3 tRCC as well as the other cancer with high-expressing circMET.
P1460 – P1884
Authors: L Grigoryan, F Haaijer-Ruskamp, J Burgerhof, J Degener, R Deschepper, D Monnet, A Matteo, E Scicluna, A Bara, C Sta ˚lsby Lundborg, J Birkin, D Berild, A Mohseni, L Diep, M Jensenius, S Ringertz, E Meyer, J Buttler, F Schwab, E Strehl, P Gastmeier, H Ruden, K De With, J Zentner, F Daschner, D Protsenko, S Yakovlev, B Gelfand, O Romashov, A Yaroshetskiy, O Ignatenko, R Seaton, D Nathwani, P Burton, E Douglas, C Rioux, P Lesprit, J Zahar, A Hulin, A Bernier-Combes, C Brun-Buisson, E Girou, Cre ´teil, P Zarb, M Borg, H Goossens, M Ferech, V Rafalskiy, R Tchilova, A Ischenko, I Toropova, I Nedorezenyuk, E Maneeva, O Suplotova, N Antonovitch, N Shevchenko
Journal: Clinical Microbiology and Infection (2006)
Vol. 54, no. 7 (July 1999), pp. 700–707, “A double‐blind, single‐dose, crossover comparison of cetirizine, ebastine, epinastine, fexofenadine, terfenadine, and loratadine versus placebo: suppression of histamine‐induced wheal and flare response for 24 h in healthy male subjects”
Journal: Allergy (1999)
Assessment of coronary stent expansion: Angiographic diameter versus intravascular ultrasound cross-sectional area: Observations from AVID Robert J. Russo, Michael J. Attubato, Charles J. Davidson, Anthony C. DeFranco, Peter J. Fitzgerald, James B. Hermiller, Robert A. Iaffaldano, Frederick S. Ling, Jennifer E. Lucisano, Patricia D. Silva, George J. Smith, S. Chiu Wong. Scripps Clinic, La Jolla, CA
Journal: Journal of the American College of Cardiology (2001)
A treatise on the chemical constitution of the brain.
Journal: JAMA (1963)

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
Calling the shots
Authors: None The Lancet Respiratory Medicine
Journal: The Lancet Respiratory Medicine (2017)

Vaccines have been one of the biggest success stories of modern medicine and WHO estimate that more than 5 million deaths were prevented annually between 2010 and 2015 owing to vaccinations delivered around the world. The 2014 Ebola epidemic—and more recently Zika—has highlighted the urgent need for vaccines to be developed against many known infectious diseases that threaten to become the next global outbreak. That scientists took the potential Ebola vaccines already available at the start of the outbreak and developed a working vaccine ready for clinical use in just over a year was an amazing feat, but it was still too late.
Common Mental Disorders and Disability Across Cultures
Authors: Johan Ormel
Journal: JAMA (1994)

<h3>Objective.</h3> —To examine the impact of common mental illness on functional disability and the cross-cultural consistency of this relationship while controlling for physical illness. A secondary objective was to determine the level of disability associated with specific psychiatric disorders. <h3>Design.</h3> —A cross-sectional sample selected by two-stage sampling. <h3>Setting.</h3> —Primary health care facilities in 14 countries covering most major cultures and languages. <h3>Patients.</h3> —A total of 25916 consecutive attenders of these facilities were screened for psychopathology using the General Health Questionnaire (96% response). Screened patients were sampled from the General Health Questionnaire score strata for the second-stage Composite International Diagnostic Interview administered to 5447 patients (62% response). <h3>Main Outcome Measures.</h3> —Patient-reported physical disability, number of disability days, and interviewer-rated occupational role functioning. <h3>Results.</h3> —After controlling for physical disease severity, psychopathology was consistently associated with increased disability. Physical disease severity was an independent, although weaker, contributor to disability. A dose-response relationship was found between severity of mental illness and disability. Disability was most prominent among patients with major depression, panic disorder, generalized anxiety, and neurasthenia; disorder-specific differences were modest after controlling for psychiatric comorbidity. Results were consistent across disability measures and across centers. <h3>Conclusions.</h3> —The consistent relationship of psychopathology and disability indicates the compelling personal and socioeconomic impact of common mental illnesses across cultures. This suggests the importance of impairments of higher-order human capacities (eg, emotion, motivation, and cognition) as determinants of functional disability. (<i>JAMA</i>. 1994;272:1741-1748)
Long-Acting Recombinant Human Interleukin-7, NT-I7, Increases Cytotoxic CD8 T Cells and Enhances Survival in Mouse Glioma Models
Authors: Jian L. Campian, Subhajit Ghosh, Vaishali Kapoor, Ran Yan, Sukrutha Thotala, Arijita Jash, Tong Hu, Anita Mahadevan, Kasem Rifai, Logan Page, Byung Ha Lee, Sara Ferrando-Martinez, Alexandra A. Wolfarth, Se Hwan Yang, Dennis Hallahan, Milan G. Chheda, Dinesh Thotala
Journal: Clinical Cancer Research (2022)

Patients with glioblastoma (GBM) are treated with radiotherapy (RT) and temozolomide (TMZ). These treatments may cause prolonged systemic lymphopenia, which itself is associated with poor outcomes. NT-I7 is a long-acting IL7 that expands CD4 and CD8 T-cell numbers in humans and mice. We tested whether NT-I7 prevents systemic lymphopenia and improves survival in mouse models of GBM.C57BL/6 mice bearing intracranial tumors (GL261 or CT2A) were treated with RT (1.8 Gy/day × 5 days), TMZ (33 mg/kg/day × 5 days), and/or NT-I7 (10 mg/kg on the final day of RT). We followed the mice for survival while serially analyzing levels of circulating T lymphocytes. We assessed regulatory T cells (Treg) and cytotoxic T lymphocytes in the tumor microenvironment, cervical lymph nodes, spleen, and thymus, and hematopoietic stem and progenitor cells in the bone marrow.GBM tumor-bearing mice treated with RT+NT-I7 increased T lymphocytes in the lymph nodes, thymus, and spleen, enhanced IFNγ production, and decreased Tregs in the tumor which was associated with a significant increase in survival. NT-I7 also enhanced central memory and effector memory CD8 T cells in lymphoid organs and tumor. Depleting CD8 T cells abrogated the effects of NT-I7. Furthermore, NT-I7 treatment decreased progenitor cells in the bone marrow.In orthotopic glioma-bearing mice, NT-I7 mitigates RT-related lymphopenia, increases cytotoxic CD8 T lymphocytes systemically and in the tumor, and improves survival. A phase I/II trial to evaluate NT-I7 in patients with high-grade gliomas is ongoing (NCT03687957).
Immunology of malaria.
Authors: Briti Sh
Journal: BMJ (1969)

PointersTumour-specific Antibodies: Over 80 % of patients with mildly disseminated melanoma had autoantibodies, these tending to disappear as dissemination progressed.There were two types, one specific for each tumour, the other for all melanoma cells (p.547).Leader at p. 543.Age and Ventilatory Capacity: Re-examination after 4 years showed a decline in the ventilatory capacity of 50-year-old Swedish men, smokers experiencing a greater decline than non-smokers (p.553).Exercise-induced Asthma: Investigation of three patients showed a " striking metabolic acidosis," which is thought to have triggered the broncho- constriction (p.556).Vitamin B12 Deficiency: Only two patients with pernicious anaemia found in 1,004 consecutive admissions to mental hospital over the age of 50 (p.559).Gastroenteritis in Maternity Hospital: Outbreak due to Salmonella virchow probably caused by carrier infecting her infant (p.561).Slow-release Fluphenazine: Severe depression may complicate treatment of schizophrenics by slow-release fluphenazine, and emphasizes need for careful psychiatric supervision (p.564).Diabetic Retinopathy: In newly diagnosed diabetics under 40 years of age the incidence of retinopathy was 1-5°o (p.567).Short Reports: Changes in regional cerebral blood flow during migraine (p.569).Abdominal tuberculosis in child in Britain (p.570).Paraplegia after repeated cardiac arrest (p.572).Rupture of choledochus cyst in pregnancy (p.573).
Prevention of renal necrosis by stress
Authors: H. Selye
Journal: JAMA (1967)

By obstructing the renal hilus for two hours with a specially constructed clip, it is possible to produce a selective necrosis affecting the medulla of the rat kidney. Despite total cessation of urine secretion, the cortex, though altered in its structure, continues to live for many weeks without producing hypertension, generalized periarteritis nodosa, or nephrosclerosis on the opposite side. In these respects as well as in its histologic structure, this "cortical kidney" differs essentially from the "endocrine kidney" elicited by permanent but partial restriction of the renal blood flow. Exposure to systemic stress (restraint, spinal-cord transection) and treatment with certain drugs (chlorpromazine hydrochloride, cyproheptadine hydrochloride) offer virtually complete protection against the macroscopic and histologic manifestations of the ischemic renal necrosis thus produced.
Constitutively active SARM1 variants that induce neuropathy are enriched in ALS patients
Authors: A. Joseph Bloom, Xianrong Mao, Amy Strickland, Yo Sasaki, Jeffrey Milbrandt, Aaron DiAntonio
Journal: Molecular Neurodegeneration (2022)

Abstract Background In response to injury, neurons activate a program of organized axon self-destruction initiated by the NAD + hydrolase, SARM1. In healthy neurons SARM1 is autoinhibited, but single amino acid changes can abolish autoinhibition leading to constitutively active SARM1 enzymes that promote degeneration when expressed in cultured neurons. Methods To investigate whether naturally occurring human variants might disrupt SARM1 autoinhibition and potentially contribute to risk for neurodegenerative disease, we assayed the enzymatic activity of all 42 rare SARM1 alleles identified among 8507 amyotrophic lateral sclerosis (ALS) patients and 9671 controls. We then intrathecally injected mice with virus expressing SARM1 constructs to test the capacity of an ALS-associated constitutively active SARM1 variant to promote neurodegeneration in vivo. Results Twelve out of 42 SARM1 missense variants or small in-frame deletions assayed exhibit constitutive NADase activity, including more than half of those that are unique to the ALS patients or that occur in multiple patients. There is a &gt; 5-fold enrichment of constitutively active variants among patients compared to controls. Expression of constitutively active ALS-associated SARM1 alleles in cultured dorsal root ganglion (DRG) neurons is pro-degenerative and cytotoxic. Intrathecal injection of an AAV expressing the common SARM1 reference allele is innocuous to mice, but a construct harboring SARM1 V184G , the constitutively active variant found most frequently among the ALS patients, causes axon loss, motor dysfunction, and sustained neuroinflammation. Conclusions These results implicate rare hypermorphic SARM1 alleles as candidate genetic risk factors for ALS and other neurodegenerative conditions.
BG9719 (CVT-124), an A1-adenosine receptor antagonist, protects against the decline in renal function observed with standard congestive heart failure therapy Stephen Gottlieb, D. Craig Brater, Ignatius Thomas, Edward Havranek, Robert Bourge, Steven Goldman, Farere Dyer, Miguel Gomez, Evan Beckman, William Abraham. Supported by Biogen, Inc., Cambridge, MA
Journal: Journal of the American College of Cardiology (2001)
Ischemia-selective early increase in nitric oxide synthesis confer acute cardioprotection against myocardial infarction afforded by pravastatin Shoji Sanada, Masafumi Kitakaze, Hiroshi Asanuma, Seiji Takashima, Koicki Node, Hisakazu Ogita, Masanori Asakura, Yulin Liao, Tsunehiko Kuzuya, Masatsugu Hori, Osaka University Graduate School of Medicine, Suita, Japan
Journal: Journal of the American College of Cardiology (2001)
Prehospital infarction angioplasty triage (PHIAT): Results from the zwolle myocardial infarction study group Nicolette Ernst, Menko Jan de Boer, Arnoud W. J. van't Hof, Frans Hollak, Jan C. A. Hoorntje, Harry Suryapranata, Jan Henk E. Dambrink, Felix Ziljstra. Isala Klinieken, hospital De Weezenlanden, Zwolle, The Netherlands
Journal: Journal of the American College of Cardiology (2001)
Abstract 211: Myocardial Hypertrophy and Circulating RNAs
Authors: Ravi V Shah, Olivia Ziegler, Kahraman Tanriverdi, Jian Rong, Martin Larson, Alexander Pico, Daniel Levy, Ramachandran S Vasan, Saumya V Das, Jane Freedman
Journal: Circulation Research (2017)

While increased left ventricular mass (LVM) is strongly associated with incident heart failure (HF), events during transition from increased LVM to HF remain unclear. Extracellular non-coding RNAs (ex-RNAs) have been implicated in cardiac hypertrophy, though whether these ex-RNAs reflect important pathways in HF in humans is underexplored. In &gt;2,000 individuals with concomitant M-mode echocardiography and ex-RNA measurements in the Framingham Heart Study, we found that lower circulating concentrations of three ex-RNAs—miR-20a-5p, miR-106b-5p, miR-17-5p—were associated with (1) greater LVM (+ one other pre-clinical phenotype, e.g., left atrial dimension or LVEDV) and (2) greater incident HF risk over a median follow-up 7.7 years ( Fig. A ). These 3 miRNAs were members of a tight cluster, regulating 883 mRNAs in common, associated with “hypertension” (OMIM) and biological process relevant to HF, including TGF-β signaling. We observed an increase in myocardial expression of these miRNAs during different phases of hypertrophy/HF development ( Fig. C, D ). Using gain and loss of function in vitro , our preliminary results suggest up-regulation of cardiomyocyte miR-106b expression abrogates expression of pathologic hypertrophy markers (ANP and BNP) during phenylephrine treatment, consistent with in silico results suggesting broad connections between miR-106b targets and natriuretic peptide signaling ( Fig. B, E-F ). These results provide translational evidence that circulating miRNAs associated with hypertrophy in patients may be protective in the transition from hypertrophy to HF at the molecular level.
Combined exposure to non-antibiotic pharmaceutics and antibiotics in the gut synergistically promote the development of multi-drug-resistance in <i>Escherichia coli</i>
Authors: Danyang Shi, Han Hao, Zilin Wei, Dong Yang, Jing Yin, Haibei Li, Zhengshan Chen, Zhongwei Yang, Tianjiao Chen, Shuqing Zhou, Haiyan Wu, Junwen Li, Min Jin
Journal: Gut Microbes (2022)

The gut microbiota represents an important reservoir of antibiotic-resistant bacteria (ARB), which poses a significant threat to public health. However, little is known about the emergence of ARB in the gut after the combined exposure to antibiotics and non-antibiotic pharmaceutics. Here, Escherichia coli, a common opportunistic pathogen in the gut microbiota, was exposed to the antidepressant duloxetine (2.5 µg/L–25 mg/L) and/or chloramphenicol (6 µg/L–4 mg/L). The resistant strains were isolated to determine the minimum inhibition concentration (MIC) of 29 antibiotics. Then, genome-wide DNA sequencing, global transcriptomic sequencing, and real-time quantitative polymerase chain reaction were performed to quantify the synergy between duloxetine and chloramphenicol. Combined exposure synergistically increased the mutation frequency of chloramphenicol resistance by 2.45–9.01 fold compared with the independent exposure. A combination index reaching 187.7 indicated strong duloxetine and chloramphenicol synergy. The resultant mutants presented heritable enhanced resistance to 12 antibiotics and became ARB to eight antibiotics. Furthermore, combined exposure significantly increased the transcriptomic expression of acrA, acrB, and marA in E. coli, and generated a more robust oxidative stress response. Together with the occurrence of DNA mutations in marR in the mutants, stronger triggers to the AcrAB-TolC transport system and the MlaFEDB ABC transporter via reactive oxygen species (ROS)-induced mutagenesis, verified by gene knockout, contributed to the synergistic enhancement of antibiotic resistance in the combined exposure group. Regardless of whether their formation was induced by duloxetine, chloramphenicol, or their combination, the E. coli mutants showed 1.1–1.7-fold increases in the expression levels of acrA, acrB, acrZ, mdtE, and mdtF. This pattern indicated that the mutants shared the same resistance mechanisms against chloramphenicol, involving the improved efflux pumps AcrAB-TolC and mdtEF. Our findings demonstrated that antibiotics and non-antibiotic pharmaceutics synergistically accelerate the evolution of ARB and may enhance their spread.
Molecular Characterization Of Opioid Receptors
Authors: H. Loh
Journal: The Annual Review of Pharmacology and Toxicology (1990)

Over the past two decades, deadly coronaviruses, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) 2019 pandemic, have majorly challenged public health. The path for virus invasion into humans and other ...Read More
Current Medical Literature
Journal: JAMA (1918)

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
Wyngaarden to leave NIH directorship in July
Authors: C. Marwick
Journal: JAMA (1989)

COME AUGUST 1, those who have long maintained that James B. Wyngaarden, MD, director of the National Institutes of Health (NIH) for the past 7 years, is indeed "the man who wasn't there" will be correct in the literal sense. Wyngaarden, will have left his job as the 12th NIH director. At the same time there are those who will be sorry to see him go. Wyngaarden already has called a special meeting of his senior staff and directors of the institutes and divisions and told them of his decision to leave. Contrary to reports that he was being forced out by the Bush administration, Wyngaarden insists that his decision to leave was his own. "I never looked for job security here," he said in an interview. "Originally, I intended to stay 5 years. Well, by August I will have been here 7 1/2 years." "Wyngaarden's appointment as director was
Clinical Chemistry, New York
Journal: JAMA (1965)

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