tbuckley/cabot-search huggingface dataset:
TRAIL-mediated apoptosis requires NF-κB inhibition and the mitochondrial permeability transition in human hepatoma cells
Authors: Young-Soo Kim, Robert F Schwabe, Ting Qian, John J Lemasters, David A Brenner
Journal: Hepatology (2002)

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a wide range of malignant cells. However, several cancers, including human hepatoma, are resistant to TRAIL. In this study, we analyzed TRAIL-induced pro- and antiapoptotic signaling pathways in human hepatoma cells. Nuclear factor kappa B (NF-kappaB) was found to be a critical TRAIL-induced antiapoptotic factor in the PLC/PRF/5, HepG2, and Hep3B cell lines. TRAIL-induced NF-kappaB activation was preceded by IkappaBalpha kinase (IKK) activation and IkappaBalpha degradation and depended on TRAF2, NF-kappaB-inducing kinase (NIK), IKK1, and IKK2. Accordingly, inhibition of NF-kappaB by adenoviral dominant negative (dn) TRAF2, NIKdn, IKK1dn, IKK2dn, or IkappaBsr sensitized PLC/PRF/5 cells to rhTRAIL, resulting in 40% to 50% cell death after 48 hours as compared with <10% with rhTRAIL alone. Agonistic anti-TRAIL receptor 1 and anti-TRAIL receptor 2 antibodies or combinations of both were equally efficient in inducing apoptosis as rhTRAIL, indicating that decoy receptors did not contribute to resistance toward TRAIL under the conditions of our study. TRAIL-mediated apoptosis depended on FADD, caspase 8 and 3 as demonstrated by the ability of FADDdn, CrmA, and pharmacologic caspase inhibitors to prevent apoptosis. Confocal microscopy showed the onset of the mitochondrial permeability transition (MPT) 5 hours after rhTRAIL plus actinomycin D, which was followed by cytochrome c release. The MPT was critical for TRAIL-induced apoptosis as demonstrated by the ability of pharmacologic MPT inhibitors to completely protect PLC/PRF/5 cells. In conclusion, NF-kappaB prevents TRAIL-induced apoptosis in human hepatoma through a TRAIL-activated TRAF2-NIK-IKK pathway. Inhibition of NF-kappaB unmasks a TRAIL-induced apoptotic signaling cascade that involves FADD, caspase 8, the MPT, and caspase 3.
Pancytopenia due to bone marrow necrosis in acute myelogenous leukemia: role of reactive CD8 cells
Authors: S.N. Markovic, R.L. Phyliky, C.Y. Li
Journal: American Journal of Hematology (1998)

Bone marrow necrosis is a rare clinical condition often associated with hematological malignancy. The mechanism by which malignant disease causes marrow necrosis is unknown. We present a case of a patient with newly diagnosed pancytopenia with bone marrow biopsy evidence of extensive marrow necrosis. Upon further work-up utilizing Tc bone scan directed bone marrow biopsy, a massive CD8+ T cell marrow infiltrate was discovered engulfing AML-M2 blasts. The role of Tc bone scans in the work-up of bone marrow necrosis as well as the potential mechanism of AML-M2 induced marrow necrosis in the setting of reactive CD8+ T cell infiltration is discussed. Am. J. Hematol. 59:74– 78, 1998. © 1998 Wiley-Liss, Inc.
Abstract 3616: Changes in signaling pathways induced by vandetanib in a human medullary thyroid carcinoma model as detected by reverse phase protein arrays
Authors: Sophie Broutin, Frederic Commo, Caroline Hego, Bérengère Marty, Corinne Dupuy, Anderson Joseph Ryan, Martin Schlumberger, Jean-Michel Bidart
Journal: Cancer Research (2010)

Abstract Introduction: Medullary thyroid carcinomas (MTC) frequently involve activating mutations in the proto-oncogene tyrosine-kinase receptor RET. Vandetanib (ZD6474, ZACTIMA) is a potent inhibitor of VEGFR-2, EGFR and RET tyrosine-kinase activities which is currently in phase III clinical trial in MTC. The aim of this study was to investigate in vitro and in vivo molecular effects of vandetanib on MTC signaling pathways using a proteomic approach based on reverse-phase protein arrays (RPPA). Methods: The human MTC TT cell line, bearing a RETC634W activating mutation, was cultured in the absence or the presence of vandetanib (100, 500, 1000 nM) for 4, 24 and 72 hours. MTC TT xenografted athymic nu/nu mice received vandetanib (50 mg/kg/day p.o.) or placebo and xenografts were removed after 1 and 4 days of treatment. Twenty-eight protein extracts from in vitro (n=24) and in vivo (n=4) experiments were profiled by RPPA analysis. Equal amounts of lysates were printed in serial dilutions onto nitrocellulose-coated glass slides. Each slide was then probed with each of a 20-antibodies set, specific for oncogenic pathways (PI3K/AKT/mTOR, MEK/p44-42, STAT3, NFKB) and cell cycle/apoptotic proteins (CDK1, PARP, cleaved-PARP). Results: In in vitro experiments, vandetanib treatment induced an increase of cleaved-PARP (p&amp;lt;10-5) with a 3-fold rise after 72 hours at 100 nM. Phosphorylation of NFKB was not significantly modified when compared to actin. In contrast, phosphorylation of STAT3 significantly decreased after 72 hours of vandetanib treatment. Overall, the MAPK signaling pathway was dramatically inhibited by vandetanib, as substantiated by the decrease of MEK and p44-42 phosphorylation when compared to their total protein forms (p&amp;lt;10-3). Inhibition of p44/42 and STAT3 phosphorylation were also observed in MTC TT xenografted mice treated by vandetanib. Several proteins were re-analyzed by western-blot analysis and the results were in agreement with those observed in RPPA. Conclusions: Together these observations demonstrated that, at the protein level, vandetanib induces apoptosis and inhibits MAPK and STAT3 pathways in MTC. Furthermore, our experimental approach confirmed the utility of protein arrays for analyzing changes in signaling pathways induced by tyrosine-kinase inhibitors. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3616.
Lenalidomide (Revlimid), Bortezomib (Velcade) and Dexamethasone (RVD) for Heavily Pretreated Relapsed or Refractory Multiple Myeloma
Authors: Victor H Jimenez-Zepeda, Donna E. Reece, Suzanne Trudel, Christine Chen, Ahmed M. Rabea, Vishal Kukreti
Journal: Blood (2010)
Fluid Intake and Urinary Tract Infection in the Elderly
Journal: JAMA (1992)

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
THE VALUE OF THE CLASSICS IN MEDICAL EDUCATION.
Journal: JAMA (1903)

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
Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain
Authors: Yi Dai, Shenglan Wang, Makoto Tominaga, Satoshi Yamamoto, Tetsuo Fukuoka, Tomohiro Higashi, Kimiko Kobayashi, Koichi Obata, Hiroki Yamanaka, Koichi Noguchi
Journal: Journal of Clinical Investigation (2007)
Diagnostic discrepancies between second-opinion and referring pathology reports of neuroendocrine tumors.
Authors: Hillary Lin, Teri A. Longacre, Vilay H. Khandelwal, Raymond R. Balise, Pamela L. Kunz
Journal: Journal of Clinical Oncology (2013)

154 Background: Neuroendocrine tumors (NETs) are rare malignancies that can arise from neuroendocrine cells throughout the body, most commonly in the lungs, gastrointestinal tract, and pancreas. The nomenclature and histologic classification schemes for NETs have historically been heterogeneous and inconsistent. Klimstra, et al published a set of NET pathology guidelines in 2010. We undertook a systematic evaluation of discrepancies between referring versus second-opinion NET pathology reports using these guidelines as our reference. Methods: We developed a cohort ofall NET cases seen at Stanford University Hospital between April 1998 and February 2012 with available Stanford and referring pathology reports for the same specimen to identify the discrepancies between their clinical diagnoses. Results: Of 141 cases, primary sites were identified as 39 (28%) pancreas, 21 (15%) small intestine, 49 (35%) other NET sites, and 32 (22%) unknown or missing. Most reports agreed on a diagnosis of NET, although twelve different terms were used to describe the NET diagnosis. There were 24 cases (17%) with major discrepancies by histologic description (NET vs. not NET). Grade, mitotic index (MI), and Ki67 were among the variables examined; they were missing from the majority of cases in one or both reports, yet more likely to be included in the Stanford report. Grade was not reported (NR) in one or both reports in 124 cases (88%); of the 17 cases reporting grade in both reports, 3 had major discrepancies. MI was NR in one or both reports in 105 cases (74%); of the 36 cases reporting MI in both reports, 5 had major discrepancies. Ki67 was NR in one or both reports in 127 cases (90%); of the 14 cases reporting Ki67 in both reports, 3 had major discrepancies. Conclusions: Clinically relevant differences were frequently found between Stanford and referring pathology reports for NETs. Our results suggest that it is beneficial for NET cases to be reviewed by NET pathology experts given the potential to impact treatment. Future studies of NET pathology discrepancies are warranted to allow additional time for adoption of the 2010 guidelines.
Cholecystostomy hazard in acute cholangitis
Authors: R. P. Saik
Journal: JAMA (1976)

Four patients with acute cholangitis were seen, all of whom died following cholecystostomy or cholecystoduodenostomy. The diagnosis of cholangitis is frequently missed in elderly patients with jaundice and sepsis. Cholecystostomy, in the face of cholangitis without documentation of patency of the cystic duct, is uniformly fatal. Diagnosis of cholangitis should be confirmed and immediately followed by adequate common duct drainage. Finally, immediate reoperation, rather than antibiotic manipulation, is advised to establish common duct drainage in those patients who do not respond to cholecystostomy within 24 hours. (<i>JAMA</i>235:2412-2413, 1976)
Errors in Author Affiliation and Funding/Support
Authors: Shinjiro Hirose
Journal: JAMA Surgery (2019)

In the Original Investigation titled "Association of O 6 -Methylguanine-DNA Methyltransferase Protein Expression With Postoperative Prognosis and Adjuvant Chemotherapeutic Benefits Among Patients With Stage II or III Gastric Cancer," 1 the authors had failed to provide citations to and description of the previously published and related 9 studies; a more complete explanation of the role of Shanghai Outdo Biotech Co, Ltd, in creating the tissue microarrays and evaluating the immunohistochemistry scores; and a better explanation of the rationale for use of R software, version 3.3.2, in the Abstract, Introduction, Methods, and eMethods 1 and eMethods 2 in the Supplement.These omissions did not affect the conclusions of the article.A Letter of Explanation 2 has been published that details the source of these errors.This article has been corrected online.
THE CODE OF ETHICS, CONSTITUTION AND BY-LAWS OF THE AMERICAN MEDICAL ASSOCIATION.
Journal: JAMA (1892)

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
England and Wales
Journal: BMJ (1925)

~~~~~~~~~~~~~~~~~~~~~~~~~~~ of William Peverill, under " Nova Placita et Novae Con- ventiones ": " Henrici Medici reddit Compotum de xxvis.et viiid.per fuga- turio.In Thesauro liberavit et quietus est."This 26s.8d.appears to have been due for the worth either of a fugitive or more probably for the worth of the goods of the absconder.In any case, Dr. Henry had paid the sum and was quit.13 Henry II (1166/67): Northants.-"Idem ViceComes reddit Compotum de xls.de Gaitintona, Radulfi Medici.In perdonis per breve Regis.Ipsi Radulfus xxxiiis.et iiiid.et debet dimidiam marcam."There was also a little matter of xxs.owing from the same Ralph from lands in Berton.This appears to have been paid, and in the following year he paid up his half-mark due from Gaitinton, buthe was not yet out of trouble, for in 1168/69, on the plea of Alan de Nevill, " Gaitintona Radulfi Medici debet iiii mareas pro iiii fabricis factis in forestam," and the debt of 4 marks appears on the roll for the next year.It does not seem ever to have been paid. 17Henry.II (1170/71): Notts and Derby.-Ilenricus
Renal failure in phenazopyridine overdose
Authors: D. A. Feinfeld
Journal: JAMA (1978)

PHENAZOPYRIDINE hydrochloride (Pyridium) is widely used for analgesia of the lower urinary tract. The drug is thought to be safe; information for the prescriber cautions only against its use in renal failure, and a standard textbook of Pharmacology does not mention nephrotoxicity (other than stone formation) or complications of overdose in its section on the drug.<sup>1</sup>We report here a case of acute tubular necrosis in a previously healthy adolescent following acute overdosage with phenazopyridine. <h3>Report of a Case</h3> A 13-year-old girl, in prior good health and with a normal developmental history, was admitted to the gastroenterology service with a 24-hour history of yellow skin color and dark urine. On the day of admission, she had had several episodes of vomiting and abdominal cramps. Initial physical findings included normal temperature, pulse rate of 80 beats per minute and regular, and blood pressure of 120/70 mm Hg with no postural
Who is receiving survivorship care plans? Findings from the 2012 LIVESTRONG survey.
Authors: Ruth Rechis, Stephanie Nutt, Carla Bann, Linda Squiers, Naveen Rao
Journal: Journal of Clinical Oncology (2013)

26 Background: There are more than 14 million cancer survivors in the US – a number that is on the rise. Care coordination resources will be essential to provide support to this growing population. Key stakeholders, including the Commission on Cancer (CoC) and the Institute of Medicine, have proposed survivorship care plans (SCPs) as a way to extend support. However, limited research has been conducted to date on SCPs. Methods: In 2012, the LIVESTRONG Foundation (LIVESTRONG) administered a survey to understand the role of a treatment summary (TS) and SCPs and how they fit into survivors’ care. Logistic regression models were conducted to identify factors associated with receiving SCPs or TS. Results: 5,303 survivors responded to these questions. While 92% of these respondents received information about where to return to for cancer check-ups, only 51% reported receiving a TS and 17% reported receiving a SCP. Survivors who were more likely to receive SCPs if they had a navigator (p&lt;.001) and if they were male, black, had finished treatment within the past year, or received care at a university-based medical center or community cancer center (p &lt; 0.05). Also, those receiving a SCP were significantly more likely to have had a detailed discussion with a provider regarding long-term side effects, emotional needs, and lifestyle recommendations. Specifically, 60% of those with a SCP discussed long-term effects compared to 39% who did not. Conclusions: Results here indicate that few survivors receive SCPs but survivors reported benefits from receiving them. Currently many workflow barriers impede delivering SCPs, and LIVESTRONG is working with key stakeholders including the CoC to automate the LIVESTRONG Care Plan powered by Penn Medicine’s OncoLink through a registry and EMR system to understand how to address this issue.
Body weight and mortality
Authors: I. A. Kashani
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The work by Dr Lee and colleagues<sup>1</sup>demonstrating a direct link between body weight and mortality and lack of greater mortality among the lean after considering the effects of illness-related weight loss and smoking<sup>2</sup>is a reminder that perhaps our messages to the public have been less than perfect. In the past two decades, the link between coronary artery disease and the quality of diet and other behaviors has been established, with emphasis on qualitative aspects of diet (eg, less fat and cholesterol). Should we have placed equal or greater emphasis on the quantitative aspects of diet? The public has been advised to consume more nuts, fish, fish oil, red wine, oat bran, and white meat, but seldom told to eat less. Even the standards for desirable body weight have been increasing over the years. Have we stopped to think that perhaps the direction of
Evaluation of tumor microenvironment and biomarkers of immune checkpoint inhibitor (ICI) response in metastatic renal cell carcinoma (mRCC).
Authors: Jason Zhu, Sarabjot Pabla, Matthew Labriola, Rajan T. Gupta, Shannon McCall, Daniel J. George, Devin Dressman, Sean Glenn, Mary Nesline, Saby George, Carl Morrison, Tian Zhang
Journal: Journal of Clinical Oncology (2019)

607 Background: ICIs are now standard of care for mRCC; however, there are few biomarkers to predict ICI response. Recent data from atezolizumab/bevacizumab trials in mRCC suggest tumors with high T eff high /PD-L1+ are more likely to respond to ICI. Here, we use this T eff gene panel as well as other markers of inflammation in the tumor microenvironment to correlate with ICI responses. Methods: This multicenter study evaluated 69 pts with mRCC treated with ICIs. FFPE tumor samples were evaluated by RNA sequencing to measure transcript levels of genes related T eff status. T eff status was defined as the mRNA expression of 17 genes (CD8, CD27, IFNG, GZMA, GZMB, PRF1, EOMES, CXCL9, CXCL10, CXCL11, CD274, CTLA4, FOXP3, TIGIT, IDO1, PSMB9, TAP1), with T eff high/low separated at the median. PD-L1 positivity was defined as ≥1% TPS based on Dako 22C3 IHC assay, and TMB high as &gt; 10 mutations per megabase. Inflamed tumors were defined as CD8 expression in the top 75th percentile compared to a large reference population of multiple tumor types. Best responses to ICI was determined by an expert radiologist using RECIST 1.1 criteria. Inflamed tumor status, T eff gene expression, PD-L1 positive, and TMB were associated with disease control (DC, defined as CR, PR, or stable disease). DC comparisons were tested using a chi-squared test with Yates’s continuity correction. Results: DC was 63% (5/8) amongst PD-L1 positive pts and 52% (31/60) in PD-L1 negative patients (p = 0.84). Only 2 pts were TMB high. The majority of mRCC tumors (97%, 67/69) were TMB low. 6-month DC in TMB high tumors was 50% (1/2) and 49.3% (33/67) in TMB low tumors (p = 1.0). 36 pts were classified as T eff high and 33 patients were classified as T eff low . 6-month DC was 61% (22/36) in the T eff high cohort and 36% (12/33) in the T eff low cohort (p = 0.069). 6-month DC was 64% of inflamed tumors (16/25) vs 41% of non-inflamed tumors (18/44) (p = 0.111). Conclusions: TMB high and PD-L1 expression do not reliably predict for DC in pts with mRCC. Utilizing a gene signature score may better predict ICI response.
Nutritional Iron Deficiency Anaemia in Wartime--II
Authors: L. S. P. Davidson, G. M. M. Donaldson, S. T. Lindsay, J. G. McSorley
Journal: BMJ (1943)

In a previous communication (Davidson et al., 1942) we reported on Part I of this investigation-the haemoglobin levels of 442 infants and pre-school children (birth to 4 years) and 389 school children (5 to 12 years).We now submit data from a more extensive survey.All the haemo- globin examinations were made under standard conditions of technique and lighting by one member of the team who has had a very wide experience and whose ability to match colours is particularly good.
Routine Use of Platelet Components Prepared with Photochemical Treatment (INTERCEPT Platelets) : Impact on Clinical Outcomes and Costs.
Authors: Jean Claude Osselaer, Chantal Doyen, Anne Sonet, Maryse Van Hooydonk, Edith Goossenaerts, Christian Chatelain, Andre Bosly, Laurence Corash
Journal: Blood (2004)
Errors in Introduction, Methods, and Discussion Sections
Authors: D Dante Yeh
Journal: JAMA Surgery (2017)

Adam M. Ali, BMBCh, MA(Cantab), MRCS(Eng); Mark D. Loeffler, MBBS, FRCS(Tr&Orth); Paul Aylin, MBChB, FFPH; Alex Bottle, PhD, MSc, HonMFPH