tbuckley/cabot-search huggingface dataset:
Prevention of Fatal Opioid Overdose
Authors: Leo Beletsky, Josiah D. Rich, Alexander Y. Walley
Journal: JAMA (2012)

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
Sulfated beef insulin treatment elicits CD8+ T cells that may abrogate immunologic insulin resistance in type I diabetes.
Authors: P Naquet, J Ellis, A Kenshole, J W Semple, T L Delovitch
Journal: Journal of Clinical Investigation (1989)

The in vitro responses of T cells from 13 insulin-nonresistant and 1 immunologically insulin-resistant (IIR) type I diabetes patients to sulfated beef insulin (SBI) were analyzed. Insulin A-loop specific CD4+ T cells from these patients did not respond to SBI. After 1 yr of treatment with SBI the IIR patient's T cell and antibody responses to beef, pork, and human insulin progressed from very high to nondetectable levels. This occurred in parallel to the appearance of her insulin-specific CD8+ T cells, which inhibited the response of her A-loop-specific CD4+ T cells to insulin. A transient increase in her CD8+ anti-insulin antibody activity coincided with a relative lack of her CD8+ T cell activity. CD8+ T cells that regulate T cell responsiveness to insulin are probably present but difficult to detect in most type I diabetes patients. These T cells were identified in only 2 of 13 insulin-nonresistant patients who presented with lipoatrophy and insulin allergy, respectively, and who possessed high-titered, anti-insulin antibodies. Our data demonstrate that CD8+ T cells play an important role in controlling peripheral tolerance to insulin and may abrogate IIR in a diabetic patient treated with SBI.
Inhibition of the DNA-Dependent Protein Kinase Catalytic Subunit Radiosensitizes Malignant Glioma Cells by Inducing Autophagy
Authors: Shigeru Daido, Akitsugu Yamamoto, Keishi Fujiwara, Raymond Sawaya, Seiji Kondo, Yasuko Kondo
Journal: Cancer Research (2005)

Abstract DNA-dependent protein kinase (DNA-PK) plays a major role in the repair of DNA double-strand breaks induced by ionizing radiation (IR). Lack of DNA-PK causes defective DNA double-strand break repair and radiosensitization. In general, the cell death induced by IR is considered to be apoptotic. On the other hand, nonapoptotic cell death, autophagy, has recently attracted attention as a novel response of cancer cells to chemotherapy and IR. Autophagy is a protein degradation system characterized by a prominent formation of double-membrane vesicles in the cytoplasm. Little is known, however, regarding the relationship between DNA-PK and IR-induced autophagy. In the present study, we used human malignant glioma M059J and M059K cells to investigate the role of DNA-PK in IR-induced apoptotic and autophagic cell death. Low-dose IR induced massive autophagic cell death in M059J cells that lack the catalytic subunit of DNA-PK (DNA-PKcs). Most M059K cells, the counterpart of M059J cells in which DNA-PKcs are expressed at normal levels, survived, and proliferated although a small portion of the cells underwent apoptosis. Low-dose IR inhibited the phosphorylation of p70S6K, a molecule downstream of the mammalian target of rapamycin associated with autophagy in M059J cells but not in M059K cells. The treatment of M059K cells with antisense oligonucleotides against DNA-PKcs caused radiation-induced autophagy and radiosensitized the cells. Furthermore, antisense oligonucleotides against DNA-PKcs radiosensitized other malignant glioma cell lines with DNA-PK activity, U373-MG and T98G, by inducing autophagy. The specific inhibition of DNA-PKcs may be promising as a new therapy to radiosensitize malignant glioma cells by inducing autophagy.
Targeting phosphatase-dependent proteoglycan switch for rheumatoid arthritis therapy
Authors: Karen M. Doody, Stephanie M. Stanford, Cristiano Sacchetti, Mattias N. D. Svensson, Charlotte H. Coles, Nikolaos Mitakidis, William B. Kiosses, Beatrix Bartok, Camille Fos, Esther Cory, Robert L. Sah, Ru Liu-Bryan, David L. Boyle, Heather A. Arnett, Tomas Mustelin, Maripat Corr, Jeffrey D. Esko, Michel L. Tremblay, Gary S. Firestein, A. Radu Aricescu, Nunzio Bottini
Journal: Science Translational Medicine (2015)

Targeting joint-lining fibroblast-like synoviocytes reduces the severity of arthritis.
Recognition of β-linked self glycolipids mediated by natural killer T cell antigen receptors
Authors: Daniel G Pellicci, Andrew J Clarke, Onisha Patel, Thierry Mallevaey, Travis Beddoe, Jérôme Le Nours, Adam P Uldrich, James McCluskey, Gurdyal S Besra, Steven A Porcelli, Laurent Gapin, Dale I Godfrey, Jamie Rossjohn
Journal: Nature Immunology (2011)
THE SYNTHESIS, STORAGE, AND EXCRETION OF CREATINE, CREATININE, AND GLYCOCYAMINE IN PROGRESSIVE MUSCULAR DYSTROPHY AND THE EFFECTS OF CERTAIN HORMONES ON THESE PROCESSES
Authors: Charles L. Hoagland, Helena Gilder, Robert E. Shank
Journal: The Journal of Experimental Medicine (1945)

The diminished excretion of creatinine in progressive muscular dystrophy is a more striking and specific phenomenon than the excess excretion of creatine, marked though this is. While creatinuria is invariably encountered in all cases of long-standing dystrophy, the extent to which the excretion of creatinine is decreased provides a more reliable indication of the severity of the disease since an excess output of creatine may occur physiologically in normal human subjects and in many pathological conditions not known to be associated with muscle disease. In progressive muscular dystrophy the residual muscle mass, as inferred from the excretion of creatinine, provides a useful index of the state of the disease at any given time. Although there is excessive creatinuria in progressive muscular dystrophy, there is no evidence that a deprivation of methyl stores occurs through a loss of urinary creatine. The loss of methyl groups contained in the excess creatine is, under ordinary conditions of diet, almost exactly compensated for by a drop in the excretion of methyl groups in the urinary creatinine. Testosterone propionate, administered over variable periods of time, resulted in the retention of creatine both in normal male children and in male children with progressive muscular dystrophy, as shown in the normal subjects by a diminution in creatine output, and in both by an excess creatinuria for variable periods of time following withdrawal of the hormone. An increase in the excretion of creatine in progressive muscular dystrophy occurred following the administration of methyl testosterone. Neither testosterone propionate nor methyl testosterone appeared to effect any consistent change in the output or urinary creatinine. No effects on the excretion of creatine and creatinine were observed following the prolonged administration of concentrate of gonadotropic and thyrotropic principles of the hypophysis, or from the administration of desoxycorticosterone acetate to patients with progressive muscular dystrophy. Except in one case, in which marked improvement was observed following the administration of testosterone propionate, no effects on the clinical course of the patients with progressive muscular dystrophy were observed as a result of treatment by any of the various hormones employed in this study.
Anchor sequence-dependent endogenous processing of human immunodeficiency virus 1 envelope glycoprotein gp160 for CD4+ T cell recognition.
Authors: M Polydefkis, S Koenig, C Flexner, E Obah, K Gebo, S Chakrabarti, P L Earl, B Moss, R F Siliciano
Journal: The Journal of Experimental Medicine (1990)

Human CD4+ T cell clones and cell lines were shown to lyse recombinant vaccinia virus-infected cells that synthesize the HIV-1 envelope glycoprotein gp160. The processing of endogenously synthesized gp160 for recognition by CD4+ T cells required that the protein, after synthesis on the rough endoplasmic reticulum and during subsequent cellular transport, remain attached to the luminal/extracellular membrane face by a hydrophobic anchor sequence.
Dasatinib Cellular Uptake and Efflux in Chronic Myeloid Leukemia Cells: Therapeutic Implications
Authors: Devendra K. Hiwase, Verity Saunders, Duncan Hewett, Amity Frede, Stephanie Zrim, Phuong Dang, Laura Eadie, L. Bik To, Junia Melo, Sharad Kumar, Timothy P. Hughes, Deborah L. White
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The organic cation transporter OCT-1 mediates active transport of imatinib. We recently showed that low OCT-1 activity is a major contributor to suboptimal response in chronic myeloid leukemia (CML) patients treated with imatinib. The relevance of OCT-1 activity and efflux pumps in determining intracellular uptake and retention (IUR) of dasatinib was assessed. Experimental Design: The effect of OCT inhibitors on [14C]dasatinib and [14C]imatinib IUR was compared using peripheral blood mononuclear cells from newly diagnosed CML patients. The role of efflux transporters was studied using ABCB1- and ABCG2-overexpressing cell lines and relevant inhibitors. Results: Unlike imatinib, there was no significant difference in the dasatinib IUR at 37°C and 4°C (P = 0.8), and OCT-1 inhibitors including prazosin did not reduce dasatinib IUR significantly. In CML mononuclear cells, prazosin inhibitable IUR was significantly higher for imatinib than dasatinib (6.38 versus 1.48 ng/200,000 cells; P = 0.002; n = 11). Patients with high OCT-1 activity based on their imatinib uptake had IC50dasatinib values equivalent to patients with low OCT-1 activity. Dasatinib IUR was significantly lower in ABCB1-overexpressing cell lines compared with parental cell lines (P &amp;lt; 0.05). PSC833 (ABCB1 inhibitor) significantly increased the dasatinib IUR (P &amp;lt; 0.05) and reduced IC50dasatinib (from 100 to 8 nmol/L) in K562-DOX cell line. The ABCG2 inhibitor Ko143 significantly increased dasatinib IUR in ABCG2-overexpressing cell lines and reduced IC50dasatinib. Conclusion: Unlike imatinib, dasatinib cellular uptake is not significantly affected by OCT-1 activity, so that expression and function of OCT-1 is unlikely to affect response to dasatinib. Dasatinib is a substrate of both efflux proteins, ABCB1 and ABCG2.
High-grade glioma before and after treatment with radiation and Avastin: Initial observations
Authors: Ingeborg Fischer, Clare H. Cunliffe, Robert J. Bollo, Shahzad Raza, David Monoky, Luis Chiriboga, Erik C. Parker, John G. Golfinos, Patrick J. Kelly, Edmond A. Knopp, Michael L. Gruber, David Zagzag, Ashwatha Narayana
Journal: Neuro-Oncology (2008)

We evaluate the effects of adjuvant treatment with the angiogenesis inhibitor Avastin (bevacizumab) on pathological tissue specimens of high-grade glioma. Tissue from five patients before and after treatment with Avastin was subjected to histological evaluation and compared to four control cases of glioma before and after similar treatment protocols not including bevacizumab. Clinical and radiographic data were reviewed. Histological analysis focused on microvessel density and vascular morphology, and expression patterns of vascular endothelial growth factor-A (VEGF-A) and the hematopoietic stem cell, mesenchymal, and cell motility markers CD34, smooth muscle actin, D2-40, and fascin. All patients with a decrease in microvessel density had a radiographic response, whereas no response was seen in the patients with increased microvessel density. Vascular morphology showed apparent "normalization" after Avastin treatment in two cases, with thin-walled and evenly distributed vessels. VEGF-A expression in tumor cells was increased in two cases and decreased in three and did not correlate with treatment response. There was a trend toward a relative increase of CD34, smooth muscle actin, D2-40, and fascin immunostaining following treatment with Avastin. Specimens from four patients with recurrent malignant gliomas before and after adjuvant treatment (not including bevacizumab) had features dissimilar from our study cases. We conclude that a change in vascular morphology can be observed following antiangiogenic treatment. There seems to be no correlation between VEGF-A expression and clinical parameters. While the phenomena we describe may not be specific to Avastin, they demonstrate the potential of tissue-based analysis for the discovery of clinically relevant treatment response biomarkers.
Further Studies on Experimental Atherosclerosis and Dietary Pyrimidines: Orotic Acid, Thiouracil, and Uracil in Male and Female Rats
Authors: LOUIS C. FILLIOS, CHIKAYUKI NAITO, STEPHEN B. ANDREWS, ALICE M. ROACH
Journal: Circulation Research (1960)

The comparative potencies of uracil nnd thiouracil in terms of thyroidal changes, hypercholesteremia, azotemia, and incipient atherosclerosis were determined in rats fed cholesterol and cholic acid. Higher dietary levels of uracil were required to produce changes similar to those seen with thiouracil. Certain dietary components related to uracil were also studied. Orotic acid was found to have a dramatic effect on female rats: it favored a markedly lower serum cholesterol level and less cardiovascular sudanophilia. When orotic acid was combined with uracil, the uracil-induced hypercholesteremia and atherogenesis were significantly inhibited, particularly in the females. Orotic acid also protected against the uracil-induced thyroid hyperplasia in these females.
A humanized non–FcR-binding anti-CD3 antibody, visilizumab, for treatment of steroid-refractory acute graft-versus-host disease
Authors: Paul A. Carpenter, Frederick R. Appelbaum, Lawrence Corey, H. Joachim Deeg, Kris Doney, Theodore Gooley, James Krueger, Paul Martin, Sandra Pavlovic, Jean Sanders, John Slattery, Daniel Levitt, Rainer Storb, Ann Woolfrey, Claudio Anasetti
Journal: Blood (2002)
THE MORPHOLOGY AND BEHAVIOR OF NEOPLASTIC MAST CELLS CULTIVATED IN VITRO
Authors: George H. Paff, Frank Bloom, Christopher Reilly
Journal: The Journal of Experimental Medicine (1947)

Fragments from two mast cell tumors of the dog have been cultured in vitro. Studies on the living and on fixed and stained preparations revealed the following: Only mast cells grew out from the original tumor fragments though these contained other types of cells. They grew in some of the roller tube cultures in a sheet resembling an epithelium but in hanging drop cultures they lay separate and were irregularly spindle or star-shaped with long protoplasmic processes. The cytoplasmic granules of the proliferating mast cells varied in size, number, and tinctorial properties. In most of the cells they stained metachromatically, in occasional cells some of the granules only could be stained, and in a few none could be stained.
Is it time to rethink the urea criterion in CURB-65?
Authors: A. V. Kamath, P. K. Myint, S. L. Vowler, B. D. W. Harrison
Journal: European Respiratory Journal (2006)

Is it time to rethink the urea criterion in CURB-65?To the Editors:We read the article by CAPELASTEGUI et al. [1] on the validation of the severity assessment rules for the management of community-acquired pneumonia (CAP) with interest.The authors concluded that CURB-65 (confusion, urea .7 mmol?L -1 , respiratory rate o30?min -1 , low systolic (,90 mmHg) or diastolic (f60 mmHg) blood pressure, and aged o65 yrs) and CRB-65 indices recommended by the British Thoracic Society are indeed useful and easy to apply in day-to-day clinical practice, thereby helping in risk stratification and management as demonstrated by LIM et al. [2].
Zebrafish as a model for leukemia and other hematopoietic disorders
Authors: Parisa Rasighaemi, Faiza Basheer, Clifford Liongue, Alister C Ward
Journal: Journal of Hematology & Oncology (2015)

Zebrafish is an established model for the study of vertebrate development, and is especially amenable for investigating hematopoiesis, where there is strong conservation of key lineages, genes, and developmental processes with humans. Over recent years, zebrafish has been increasingly utilized as a model for a range of human hematopoietic diseases, including malignancies. This review provides an overview of zebrafish hematopoiesis and describes its application as a model of leukemia and other hematopoietic disorders.
A Lecture on the Tubercle-Bacillus and Phthisis
Authors: T. H. Green
Journal: BMJ (1883)

doctors, except the last who had been consulted about him, that the patient was a man of naturally delicate constitution, that he needed constant keeping up, and that his chances of life were in direct proportion to the amount of support that he could take.Accordingly, he was taking food and wine every second hour, hadl iron, quinine and strychnia three times daily, and, being increasingly thirsty, he drank milk and soda-water without much regard to fre- quency and amount.Questioned as to my opinion of the patient's malady, and urged by my colleagues to say exactly what I thought, I replied that he was a man with deteriorated, but not seriously diseased tissues and organs, and that he was in peril of death, not so much from his malady, as from the means used for its cure; that he was being poisoned by food and wine, that he was in the condition of a fire having more coals put upon it than it could burn, and that his chimneys being choked, he was in near danger of being suffocated with his own smoke.My colleagues agreeing with this view of the case, and the patient, after much discussion and explanation, assenting, he was placed upon a precise and severe regimen.He was ordered to have four
Short-term effects of nasal proportional assist ventilation in patients with chronic hypercapnic respiratory insufficiency
Authors: N Ambrosino, M Vitacca, G Polese, M Pagani, K Foglio, A Rossi
Journal: European Respiratory Journal (1997)

Proportional assist ventilation (PAV) has recently been proposed as a mode of synchronized partial ventilatory support. This study evaluates the short-term effects of nasal PAV on arterial blood gases in stable patients with chronic hypercapnia. Forty two patients (30 with chronic obstructive pulmonary disease (COPD) and 12 with restrictive chest wall disease (RCWD) due to kyphoscoliosis) underwent a 1 h run of nasal PAV. Randomly, two levels of assistance were performed: 1) PAV was set at a level corresponding to volume assist (VA) and flow assist (FA) at 80% of the individual values of elastance (Ers) and resistance (Rrs) obtained with the "runaway" method; and 2) VA and FA were set at a value corresponding to the difference between the patients' individual Ers and Rrs and normal values of Ers and Rrs. Arterial blood gases and dyspnoea (by visual analogue scale (VAS)) were evaluated in all patients during unsupported ventilation and 60 min of PAV. PAV was well tolerated and resulted in significant improvement in arterial oxygen tension (Pa,O2), arterial carbon dioxide tension (Pa,CO2) (6.8+/-0.8 to 7.4+/-1.4 and 7.2/-0.9 to 6.8+/-0.9 kPa, respectively) and VAS (29+/-23 to 20+/-18%). The effects of PAV were not different in the two groups of diseases nor in the two groups of settings. Different settings of nasal proportional assist ventilation are well tolerated and may improve gas exchange and dyspnoea in patients with stable hypercapnic respiratory insufficiency.
Erratum to “Transient restoration of anti-viral T cell responses induced by lamivudine therapy in chronic hepatitis B”
Authors: Carolina Boni, Amalia Penna, Antonio Bertoletti, Vincenzo Lamonaca, Irene Rapti, Gabriele Missale, Massimo Pilli, Simona Urbani, Albertina Cavalli, Simona Cerioni, Ruggero Panebianco, Julian Jenkins, Carlo Ferrari
Journal: Journal of Hepatology (2004)
Three vs Twelve Months of Dual Antiplatelet Therapy After Zotarolimus-Eluting Stents
Authors: Fausto Feres
Journal: JAMA (2013)

The current recommendation is for at least 12 months of dual antiplatelet therapy after implantation of a drug-eluting stent. However, the optimal duration of dual antiplatelet therapy with specific types of drug-eluting stents remains unknown.To assess the clinical noninferiority of 3 months (short-term) vs 12 months (long-term) of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) with zotarolimus-eluting stents.The OPTIMIZE trial was an open-label, active-controlled, 1:1 randomized noninferiority study including 3119 patients in 33 sites in Brazil between April 2010 and March 2012. Clinical follow-up was performed at 1, 3, 6, and 12 months. Eligible patients were those with stable coronary artery disease or history of low-risk acute coronary syndrome (ACS) undergoing PCI with zotarolimus-eluting stents.After PCI with zotarolimus-eluting stents, patients were prescribed aspirin (100-200 mg daily) and clopidogrel (75 mg daily) for 3 months (n = 1563) or 12 months (n = 1556), unless contraindicated because of occurrence of an end point.The primary end point was net adverse clinical and cerebral events (NACCE; a composite of all-cause death, myocardial infarction [MI], stroke, or major bleeding); the expected event rate at 1 year was 9%, with a noninferiority margin of 2.7%. Secondary end points were major adverse cardiac events (MACE; a composite of all-cause death, MI, emergent coronary artery bypass graft surgery, or target lesion revascularization) and Academic Research Consortium definite or probable stent thrombosis.NACCE occurred in 93 patients receiving short-term and 90 patients receiving long-term therapy (6.0% vs 5.8%, respectively; risk difference, 0.17 [95% CI, -1.52 to 1.86]; P = .002 for noninferiority). Kaplan-Meier estimates demonstrated MACE rates at 1 year of 8.3% (128) in the short-term group and 7.4% (114) in the long-term group (HR, 1.12 [95% CI, 0.87-1.45]). Between 91 and 360 days, no statistically significant association was observed for NACCE (39 [2.6%] vs 38 [2.6%] for the short- and long-term groups, respectively; HR, 1.03 [95% CI, 0.66-1.60]), MACE (78 [5.3%] vs 64 [4.3%]; HR, 1.22 [95% CI, 0.88-1.70]), or stent thrombosis (4 [0.3%] vs 1 [0.1%]; HR, 3.97 [95% CI, 0.44-35.49]).In patients with stable coronary artery disease or low-risk ACS treated with zotarolimus-eluting stents, 3 months of dual antiplatelet therapy was noninferior to 12 months for NACCE, without significantly increasing the risk of stent thrombosis.clinicaltrials.gov Identifier: NCT01113372.
A New Strategy for Discontinuation of Dual Antiplatelet Therapy
Authors: Byeong-Keuk Kim, Myeong-Ki Hong, Dong-Ho Shin, Chung-Mo Nam, Jung-Sun Kim, Young-Guk Ko, Donghoon Choi, Tae-Soo Kang, Byoung-Eun Park, Woong-Chol Kang, Seung-Hwan Lee, Jung-Han Yoon, Bum-Kee Hong, Hyuck-Moon Kwon, Yangsoo Jang
Journal: Journal of the American College of Cardiology (2012)
Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial
Authors: Pedro Cahn, Jaime Andrade-Villanueva, José R Arribas, José M Gatell, Javier R Lama, Michael Norton, Patricia Patterson, Juan Sierra Madero, Omar Sued, Maria Inés Figueroa, Maria José Rolon
Journal: The Lancet Infectious Diseases (2014)