tbuckley/cabot-search huggingface dataset:
Endogenous intrahepatic IFNs and association with IFN-free HCV treatment outcome
Authors: Eric G. Meissner, David Wu, Anu Osinusi, Dimitra Bon, Kimmo Virtaneva, Dan Sturdevant, Steve Porcella, Honghui Wang, Eva Herrmann, John McHutchison, Anthony F. Suffredini, Michael Polis, Stephen Hewitt, Ludmila Prokunina-Olsson, Henry Masur, Anthony S. Fauci, Shyamasundaran Kottilil
Journal: Journal of Clinical Investigation (2014)

BACKGROUND. Hepatitis C virus (HCV) infects approximately 170 million people worldwide and may lead to cirrhosis and hepatocellular carcinoma in chronically infected individuals. Treatment is rapidly evolving from IFN-α–based therapies to IFN-α–free regimens that consist of directly acting antiviral agents (DAAs), which demonstrate improved efficacy and tolerability in clinical trials. Virologic relapse after DAA therapy is a common cause of treatment failure; however, it is not clear why relapse occurs or whether certain individuals are more prone to recurrent viremia.
US healthcare continues to lag behind other countries despite double the costs
Authors: B. Roehr
Journal: BMJ (2010)

The US healthcare system has glaring gaps where it falls far behind other countries in terms of access, quality, efficiency, and health outcomes, according to the International Health Policy Survey.

The 13th annual version of the report by the charity the Commonwealth Fund was released on 18 November in Washington, DC at an international symposium that brings together experts in healthcare to foster cross national research and collaboration. The paper was published in the journal Health Affairs. 

Karen Davis, president of the fund, said, “The US spends far more, more than $7500 (£4650; €5470) per capita in 2008, more than twice, on average, what other countries spend that cover everyone.”

The rate of spending increases “are on a continuing upward …
Transactivation of the Epidermal Growth Factor Receptor by Formylpeptide Receptor Exacerbates the Malignant Behavior of Human Glioblastoma Cells
Authors: Jian Huang, Jinyue Hu, Xiuwu Bian, Keqiang Chen, Wanghua Gong, Nancy M. Dunlop, O.M. Zack Howard, Ji Ming Wang
Journal: Cancer Research (2007)

Abstract The G protein-coupled formylpeptide receptor (FPR), which mediates leukocyte migration in response to bacterial and host-derived chemotactic peptides, promotes the chemotaxis, survival, and tumorigenesis of highly malignant human glioblastoma cells. Because glioblastoma cells may also express other receptors for growth signals, such as the epidermal growth factor (EGF) receptor (EGFR), we investigated the role of EGFR in the signaling cascade of FPR and how two receptors cross-talk to exacerbate tumor growth. We found that N-formyl-methionyl-leucyl-phenylalanine, an FPR agonist peptide, rapidly induced EGFR phosphorylation at tyrosine residue (Tyr) 992, but not residues 846, 1068, or 1173, in glioblastoma cells, whereas all these residues were phosphorylated after only EGF treatment. The FPR agonist-induced EGFR phosphorylation in tumor cells was dependent on the presence of FPR as well as Gαi proteins, and was controlled by Src tyrosine kinase. The transactivation of EGFR contributes to the biological function of FPR in glioblastoma cells because inhibition of EGFR phosphorylation significantly reduced FPR agonist-induced tumor cell chemotaxis and proliferation. Furthermore, depletion of both FPR and EGFR by short interference RNA abolished the tumorigenesis of the glioblastoma cells. Our study indicates that the glioblastoma-promoting activity of FPR is mediated in part by transactivation of EGFR and the cross-talk between two receptors exacerbates the malignant phenotype of tumor cells. Thus, targeting both receptors may yield antiglioblastoma agents superior to those targeting one of them. [Cancer Res 2007;67(12):5906–13]
Percutaneous Transhepatic Cholangiography
Authors: Allan G. Redeker
Journal: JAMA (1975)

RECENT reports from Japan describing percutaneous transhepatic cholangiography (PTC) with a new, thin needle have suggested this technique to be unusually reliable and safe.<sup>1</sup>We have performed PTC with the "Chiba needle" in 40 patients with suspected biliary tract obstruction or jaundice of uncertain cause. <h3>Procedure</h3> The needles used in this procedure were developed at Chiba University, Chiba, Japan. This very flexible needle with stylet is made of steel, 15 to 17 cm long and 0.7 mm in diameter. A radiopaque marker (coin) was placed on the xiphoid process. The needle entry site was usually in the midaxillary line at the level of the eighth or ninth intercostal space. The needle was inserted parallel to the x-ray table, attempting to position its tip just under the coin marker but not beyond the midvertebral line. Throughout the procedure the patients were permitted normal respiration. After removing the stylet, contrast medium was
Perioperative blockade: guidelines do not reflect the problems with the evidence from the DECREASE trials
Authors: G. D. Cole, D. P. Francis
Journal: BMJ (2014)

The trials underpinning initiation of perioperative β blockers in patients with ischaemic heart disease having high risk surgery have largely been discredited, and the remaining evidence points to an increased risk of death. However, changes to the European guidelines have been slow. <b>Graham Cole</b> and <b>Darrel Francis</b> call for improvements to permit guideline experts to perform rapid amendments when required
SATIRE
Authors: William Keith C. Morgan
Journal: JAMA (1967)

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
Platelet Membrane Receptor Glycoprotein IIb/IIIa Antagonism in Unstable Angina
Authors: Pierre The´roux, Simon Kouz, Louis Roy, Merril L. Knudtson, Jean G. Diodati, Jean-Franc¸ois Marquis, James Nasmith, Anthony Y. Fung, Jean-Rock Boudreault, Franc¸ois Delage, Robert Dupuis, Catherine Kells, Marianne Bokslag, Beat Steiner, Hans J. Rapold
Journal: Circulation (1996)

Background Ligand binding to the platelet membrane receptor glycoprotein (GP) IIb/IIIa, the final and obligatory step to platelet aggregation, can now be inhibited by pharmacological agents. This study was designed to evaluate the potential of lamifiban, a novel nonpeptide antagonist of GP IIb/IIIa, for the management of unstable angina. Methods and Results In a prospective, dose-ranging, double-blind study, 365 patients with unstable angina were randomized to an infusion of 1, 2, 4, or 5 μg/min of lamifiban or of placebo. Treatment was administered for 72 to 120 hours. Outcome events were measured during the infusion period and after 1 month. Concomitant aspirin was administered to all patients and heparin to 28% of patients. Lamifiban, all doses combined, reduced the risk of death, nonfatal myocardial infarction, or the need for an urgent revascularization during the infusion period from 8.1% to 3.3% ( P =.04). The rates were 2.5%, 4.9%, 3.3%, and 2.4% with increasing doses. At 1 month, death or nonfatal infarction occurred in 8.1% of patients with placebo and in 2.5% of patients with the two high doses ( P =.03). The highest dose of lamifiban additionally prevented the need for an urgent intervention. Lamifiban dose-dependently inhibited platelet aggregation. Bleeding times were significantly prolonged with platelet inhibition of &gt;80%. Major (but neither life-threatening nor intracranial) bleedings occurred in 0.8% of patients with placebo and 2.9% with lamifiban. Conclusions The nonpeptide GP IIb/IIIa antagonist lamifiban protected patients with unstable angina from severe ischemic events during a 3- to 5-day infusion and reduced the incidence of death and infarction at 1 month, suggesting considerable promise for this new therapeutic approach.
A woman with generalised weakness, hypokalaemia, and metabolic acidosis
Authors: H. U. Rehman
Journal: BMJ (2012)

A 31 year old woman presented with generalised weakness and muscle pain a week after having a flu-like illness, which had resolved completely. She had no diarrhoea, vomiting, urinary symptoms, joint pains, rashes, dry eyes, or dry mouth. Her medical history was unremarkable. Physical examination showed that she was well hydrated. Blood pressure was 102/55 mm Hg, pulse rate 88 beats/min. Muscle strength was 4/5 and 0/5 in the flexor muscle groups and 1/5 and 4/5 in the extensor muscle groups of the upper limbs and lower limbs, respectively. Deep tendon reflexes were brisk in the upper and lower limbs. No sensory deficit was found and the Babinski reflex test was negative. The rest of the physical examination was unremarkable.

Initial blood results were sodium 141 mmol/L (normal range 135-145), potassium 1.7 mmol/L (3.5-5.0), chloride 118 mmol/L (98-110), carbon dioxide 14 mmol/L (21-30), anion gap 11 mmol/L (10-20), urea 5.4 mmol/L (3.0-7.1), creatinine 69 µmol/L (60-130), creatine kinase 320 U/L (30-135). Urine results were pH 7.00 (5.0-8.0), sodium 47 mmol/L, potassium 13.2 mmol/L, chloride 52 mmol/L, calcium 1.50 mmol/L, and creatinine 3.9 mmol/L. Arterial blood gases on room air showed pH 7.31 (7.35-7.45), partial pressure of carbon dioxide 26 mm Hg (33-45), partial pressure of oxygen 111 mm Hg (75-100), bicarbonate 15 mmol/L (22-26), and base excess −12.1 mmol/L (−2.5 to 2.5). Erythrocyte sedimentation rate was 106 mm in the first hour (0-20). Complete blood count, thyroid function tests, and liver panel were normal.

She had a polyclonal increase in gammaglobulins 24.5g (6.0-18.0), IgG of 27.90 g …
Effective diagnosis of genetic disease by computational phenotype analysis of the disease-associated genome
Authors: Tomasz Zemojtel, Sebastian Köhler, Luisa Mackenroth, Marten Jäger, Jochen Hecht, Peter Krawitz, Luitgard Graul-Neumann, Sandra Doelken, Nadja Ehmke, Malte Spielmann, Nancy Christine Øien, Michal R. Schweiger, Ulrike Krüger, Götz Frommer, Björn Fischer, Uwe Kornak, Ricarda Flöttmann, Amin Ardeshirdavani, Yves Moreau, Suzanna E. Lewis, Melissa Haendel, Damian Smedley, Denise Horn, Stefan Mundlos, Peter N. Robinson
Journal: Science Translational Medicine (2014)

Patients with genetic disease of unknown causes can be rapidly diagnosed by bioinformatic analysis of disease-associated DNA sequences and phenotype.
Genetic mosaicism: what Gregor Mendel didn't know.
Authors: R Hirschhorn
Journal: Journal of Clinical Investigation (1995)

The word "mosaic" was originally used as an adjective to describe any form of work or art produced by the joining to- gether of many tiny pieces that differ in size and color (1).In that sense, virtually all multicellular organisms are mosaics of cells of different form and function.Normal developmentally determined mosaicism can involve permanent alterations of DNA in somatic cells such as the specialized cells of the im- mune system.In such specialized somatic cells, different re- arrangements of germ line DNA for immunoglobulin and T cell receptor genes and the different mutations accompanying these rearrangements alter DNA and function.However, these alter- ations in individual cells cannot be transmitted to offspring since they occur only in differentiated somatic cells.Another form of normal mosaicism occurs in females.Virtually all mam- malian females are mosaic with respect to their X chromosomes.
In-vivo proton-decoupled 31P-magnetic resonance spectroscopic imaging for the determination of altered phosphoethanolamine levels in alcoholic liver disease
Authors: Heinz-Peter Schlemmer, Ines Dornacher, Tamara Sawatzki, Martin Hellenschmidt, Peter Bachert, Gerhard van Kaic, Helmut K. Seitz
Journal: Journal of Hepatology (2002)
Interleukin 2 abrogates the nonresponsive state of T cells expressing a forbidden T cell receptor repertoire and induces autoimmune disease in neonatally thymectomized mice.
Authors: J L Andreu-Sánchez, I M Moreno de Alborán, M A Marcos, A Sánchez-Movilla, C Martínez-A, G Kroemer
Journal: The Journal of Experimental Medicine (1991)

Under physiological conditions, the vast majority of T cells differentiate in the thymus, an organ that provides an optimal microenvironment for T cell maturation and shapes the T cell repertoire via positive and negative selection processes. In the present report, we demonstrate that neonatal thymectomy of CBA/H mice results in a diminution of T cells in peripheral lymphoid organs (spleen, lymph nodes), but is followed by a marked transient (12 wk) increase in Thy-1+ CD3+ cells in the peritoneal cavity. These cells exhibit predominantly a double-negative (CD4-CD8-) phenotype among which products of the T cell receptor (TCR) V beta 11 gene family (i.e., an I-E-reactive TCR normally deleted in I-E-bearing CBA/H mice) are selectively overexpressed. This observation suggests that, under athymic conditions, T cell differentiation and/or accumulation may occur in the peritoneal cavity. Intraperitoneal inoculation of an interleukin 2 (IL-2) vaccinia virus construct that releases high titers of human IL-2 in vivo induces conversion of these double-negative T cells to either CD4+ CD8- or CD4- CD8+ single positives, and allows in vitro stimulation of TCR V beta 11-bearing cells with a clonotypic anti-V beta antibody. Since IL-2 induces autoimmune manifestations (DNA autoantibodies, rheumatoid factors, and interstitial nephritis) in thymectomized CBA/H mice, but not in sham-treated littermates, this lymphokine is likely to enhance the autoaggressive function of T cells that bear forbidden, potentially autoreactive TCR gene products and that are normally deleted in the thymus.
The Rise and Fall of Epidemiology, 1950–2000 A.D.
Authors: Kenneth J. Rothman
Journal: New England Journal of Medicine (1981)

IN 1662 John Graunt, a London haberdasher, published his magnum opus, Natural and Political Observations... Made upon the Bills of Mortality, and thereby established the field of epidemiology.1 Graunt brought to light a diversity of facts about human life and disease that had not previously been appreciated. He was the first to notice that the numbers of births and deaths of males exceeded those of females (by the ratio of 14 to 13); he noticed, too, that despite their greater mortality, men had less morbidity than women. Graunt quantified for the first time the high mortality in children, noting that . . .
Unique Aspects of Heart and Lung Transplantation Exhibited in the 'Domino-Donor' Operation
Authors: William A. Baumgartner
Journal: JAMA (1989)

During the past 2 decades various refinements in heart and lung transplantation procedures have taken place. Improved preservation methods, new immunosuppressive medications, and advances in technical capabilities have allowed innovative procedures to be performed. In May 1987 the first "domino-donor" operation was performed in the United States. A 28-year-old man with cystic fibrosis and end-stage lung disease received the heart and lungs of an anonymous donor after he donated his heart to a 38-year-old man with end-stage ischemic cardiomyopathy. The technical and logistical aspects of this transplantation procedure are described herein. Other unusual features of this case that are discussed include heart-lung transplantation for a patient with cystic fibrosis, the use of cardiopulmonary bypass to allow lung procurement and transplantation across long distances, and the current role of heterotopic cardiac transplantation.
Clinical Comparison of Two Agents Used In Brain Scanning
Authors: John Mealey, John R. Dehner, Isaac C. Reese
Journal: JAMA (1964)

Sixty-three patients with suspected intracranial lesions were scanned with both chlormerodrin Hg 203 (Neohydrin) and radio-iodinated serum albumin (Risa). Scans were read as unknowns and were compared for accuracy and overall quality. Results in 23 patients with tumors, two with abscesses and seven with hematomas, were nearly identical. Both agents correctly localized 78% or missed the same neoplasms. There were no false-positive studies in 31 patients, without evidence of intracranial space-taking lesions. This study suggests that brain scanning be performed initially with chlormerodrin Hg 203, largely because of the temporal convenience. If interpretation of the chlormerodrin Hg 203 scans is equivocal, scanning with radio-iodinated serum albumin at 24 and 48 hours is recommended.
Therapeutic DNA Vaccination Using In Vivo Electroporation Followed by Standard of Care Therapy in Patients With Genotype 1 Chronic Hepatitis C
Authors: Ola Weiland, Gustaf Ahlén, Helmut Diepolder, Maria-Christina Jung, Sepideh Levander, Michael Fons, Iacob Mathiesen, Niranjan Y Sardesai, Anders Vahlne, Lars Frelin, Matti Sällberg
Journal: Molecular Therapy (2013)

Clearance of infections caused by the hepatitis C virus (HCV) correlates with HCV-specific T cell function. We therefore evaluated therapeutic vaccination in 12 patients with chronic HCV infection. Eight patients also underwent a subsequent standard-of-care (SOC) therapy with pegylated interferon (IFN) and ribavirin. The phase I/IIa clinical trial was performed in treatment naive HCV genotype 1 patients, receiving four monthly vaccinations in the deltoid muscles with 167, 500, or 1,500 μg codon-optimized HCV nonstructural (NS) 3/4A-expressing DNA vaccine delivered by in vivo electroporation (EP). Enrollment was done with 2 weeks interval between patients for safety reasons. Treatment was safe and well tolerated. The vaccinations significantly improved IFN-γ-producing responses to HCV NS3 during the first 6 weeks of therapy. Five patients experienced 2-10 weeks 0.6-2.4 log10 reduction in serum HCV RNA. Six out of eight patients starting SOC therapy within 1-30 months after the last vaccine dose were cured. This first-in-man therapeutic HCV DNA vaccine study with the vaccine delivered by in vivo EP shows transient effects in patients with chronic HCV genotype 1 infection. The interesting result noted after SOC therapy suggests that therapeutic vaccination can be explored in a combination with SOC treatment.
Hypothyroidism minimizes liver damage and improves survival in rats with thioacetamide induced fulminant hepatic failure
Authors: Rafael Bruck, Ran Oren, Haim Shirin, Hussein Aeed, Moshe Papa, Zipora Matas, Liliana Zaidel, Yona Avni, Zamir Halpern
Journal: Hepatology (1998)

Recent data from animal studies suggest that induced hypothyroidism prevents the hyperdynamic circulation in portal vein ligated rats, liver cirrhosis in rats chronically treated with thioacetamide (TAA), and immune-mediated acute liver injury induced in mice by concanavalin A. Therefore, the aim of this present study is to determine whether hypothyroidism would likewise prevent fulminant hepatic failure (FHF) in rats. FHF was induced by 3 consecutive ip injections of TAA (400 mg/kg) at 24-hour intervals. Hypothyroidism was induced in rats by either methimazole (MMI) or propylthiouracil (PTU) and surgical thyroidectomy and was confirmed by elevated serum thyroid stimulating hormone levels. Serum levels of liver enzymes, blood ammonia, and prothrombin time were significantly lower in all 3 groups of hypothyroid rats. The stage of hepatic encephalopathy (HE) and the survival rates were significantly improved in the hypothyroid rats (P < .01); the histologic examination of their livers showed less necrosis and inflammation (P < .01). In the hypothyroid rats, the serum levels of malondialdehyde 48 hours after thioacetamide (TAA) administration were lower than in control rats (P < .01). Exogenous supplementation of hypothyroid rats with L-thyroxine started 48 hours before TAA administration abrogated the protective effects of hypothyroidism. The serum levels of tumor necrosis factor alfa (TNF-alpha), interleukin (IL) 2 and IL-6 after 24 hours were slightly lower in the hypothyroid rats, but the administration of soluble receptor of TNF (10-1,000 microg/rat) did not prevent the induction of fulminant liver failure by TAA. Oxygen extraction, studied in isolated perfused liver preparation, was significantly lower in livers of hypothyroid rats (P < .01). These results suggest that induced hypothyroidism decreases the development of liver injury in a rat model of FHF. The mechanism may involve diminished oxidative cell injury caused by decreased oxygen utilization and hypometabolism associated with hypothyroidism.
Abstract B30: Regulation of angiogenesis by the VEGF/miR-101/EZH2 axis
Authors: Michiel Smits, Shahryar E. Mir, Jonas Nilsson, Petra van der Stoop, Anneke Niers, Victor Marquez, Jacqueline Cloos, Xandra Breakefield, Anna Krichevsky, David Noske, Bakhos Tannous, Thomas Wurdinger
Journal: Clinical Cancer Research (2010)

Abstract Rationale: Angiogenesis is a balanced process controlled by pro- and anti-angiogenic molecules of which the regulation is not yet fully understood. Besides classical gene regulation, miRNAs have emerged as post-transcriptional regulators of angiogenesis. In addition, epigenetic changes caused by histone modifying enzymes have emerged as modulators of angiogenesis as well. So far, the interplay between miRNA modulation and histone-modulating enzymes during angiogenesis is unclear. Objective: To investigate the functions of miR-101 and of its target, the histone methyltransferase EZH2 in endothelial cells and angiogenesis. Methods and Results: We show that the pro-angiogenic effects caused by VEGF-mediated down-regulation of miR-101 are partly mediated through reduced translational repression of the histone methyltransferase EZH2. In vitro, the sprouting and migratory properties of primary endothelial cell cultures were reduced by inhibiting EZH2 through up-regulation of miR-101, siRNA-mediated knockdown of EZH2, or treatment with 3-Deazaneplanocin A (DZNep), a small molecule inhibitor of EZH2 methyltransferase activity. In addition, we studied the effects of EZH2 inhibition on tumor angiogenesis in vivo. We found that systemic DZNep administration reduced the number of blood vessels in a subcutaneous glioblastoma mouse model, without showing adverse toxicities. Conclusion: By determining a pro-angiogenic VEGF/miR-101/EZH2 axis in endothelial cells we provide evidence that there is a functional link between growth factor-mediated signaling, post-transcriptional silencing, and histone methylation in the angiogenesis process. Inhibition of EZH2 may prove therapeutical in diseases in which aberrant vascularization plays a role. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B30