tbuckley/cabot-search huggingface dataset:
06.02 Ex vivo functional comparison of baricitinib and tofacitinib for cytokine signalling in human leukocyte subpopulations
Authors: Iain McInnes, Richard Higgs, Guilherme Rocha, Xin Zhang, Jonathan Lee, Thomas Wehrman, William Macias, Steven Zuckerman, Peter Taylor, Maurizio Gentile
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Baricitinib (bari) and tofacitinib (tofa) are selective JANUS kinase inhibitors (JAKi). In biochemical assays, bari exhibits greatest potency against JAK1 and JAK2, whereas that for tofa is against JAK1 and JAK3. The objective was to determine whether differences in JAKi specificity translate to differences in cellular signal transduction in leukocyte subpopulations stimulated by cytokines, indicated by inhibition of signal transducers of activator transcription (STATs) phosphorylation. <h3>Materials and methods</h3> Peripheral blood mononuclear cells (PBMC) were obtained from healthy donors (n=6). Leukocyte preparations were incubated with JAKi using a 7 point dose range, 2.44–10,000 nM, for 1 hour before cytokine stimulation. The half maximum inhibitory concentration (IC<sub>50</sub>) values were determined by plotting the mean fluorescence intensity of cytokine-stimulated and nonstimulated samples in phenotypically gated leukocyte subpopulations.<sup>1</sup> <h3>Results</h3> IC<sub>50</sub> values for bari and tofa were similar for interleukin (IL)−6 across leukocyte subsets. Differences were observed for other cytokines. The IC<sub>50</sub> across leukocyte subpopulations stimulated with the same cytokine varied 2–3 fold per compound. The most significant differences between JAKi IC<sub>50</sub> values were for cytokines that use JAK1/3. Tofa was a more potent inhibitor of IL-2, IL-4, IL-15, and IL-21 induced STAT phosphorylation than bari. Both compounds inhibited IL-10 stimulation of phosphorylated STAT3 (pSTAT3) and interferon (IFN)-α stimulation of pSTAT1, pSTAT3, and pSTAT5 similarly. Inhibition of IFNα pSTAT3 and pSTAT5 were similar for both JAKi, although less potent in inhibiting STAT1 phosphorylation. Bari and tofa inhibited granulocyte–macrophage colony-stimulating factor (JAK2) and granulocyte colony-stimulating factor and IFNγ signalling, with bari exhibiting a greater effect in monocytes than tofa. <h3>Conclusions</h3> The differences in IC<sub>50</sub> for key cytokine stimuli suggest fundamental functional differences across classes of JAKi. The potency of JAKi varied between different leukocyte subpopulations and is STAT substrate dependent. At the clinical level, therefore, these agents should not be considered biologically equivalent. A practical consequence is that determination of JAKi potency on IC<sub>50</sub> based solely on a nongated whole blood assay would not detect differential responses of leukocyte subpopulations by JAKi. <h3>Acknowledgment</h3> Original abstract (c) by EULAR/BMJ. First presented at 'EULAR 2016' and published in 10.1136/annrheumdis-2016-eular.1512. Any reprints, promotional options, education material etc have to be done through the original source (ARD/BMJ). <h3>Reference</h3> 1.Krutzik, et al. Nat Methods. 2006;3(5):361–368.
A NEW SIGN FOR THE DIAGNOSIS OF PERICARDITIS WITH EFFUSION IN CHILDREN
Journal: JAMA (1921)

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
National, State, and Urban Area Vaccination Levels Among Children Aged 19-35 Months--United States, 2002
Journal: JAMA (2003)

Each annual birth cohort in the United States comprises approximately four million infants. Maintaining the gains in childhood vaccination coverage achieved during the 1990s among these children poses an ongoing challenge for public health. The National Immunization Survey (NIS) provides annual estimates of vaccination coverage among children aged 19-35 months for each of the 50 states and 28 selected urban areas. This report presents NIS findings for 2002, which indicate a marked nationwide increase in coverage with >/=1 dose of varicella vaccine (VAR), substantial uptake for >/=3 doses of pneumococcal conjugate vaccine (PCV), generally steady coverage levels for other vaccines nationwide, and continued wide variability in coverage among the states and selected urban areas.
THE ENDOCRINE SOCIETY LAUREATE AWARDS
Authors: Liam Crowley, Gerald Reaven, John Baxter, ; Larsen, ; Jameson, Kathryn Horwitz, Oppenheimer Ernst, Steven Kliewer, Charis Eng, Rohit Kulkarni, Joel Elmquist, Randy Seeley, Constantine Stratakis, Wiebke Arlt
Journal: Endocrine Reviews (2010)
French Sanitary Commissioner at Constantinople.
Journal: JAMA (1893)

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
Long Term Infectious Complications Following Reduced Intensity Conditioning (RIC)Allogeneic HLA-Identical Sibling Transplantation (allo-SCT).
Authors: A. Etienne, M. Mohty, C. Faucher, M. Ferrando, R. Benramdane, C. Zandotti, L. Collet, N. Vey, A.M. Stoppa, D. Coso, P. Viens, J.A. Gastaut, D. Blaise
Journal: Blood (2004)
Restriction of V beta gene usage of liver-derived lymphocytes in chronic hepatitis B and C . Service d'H�matologie et Immunologie, Service d'H�patologie, Service d'Anatomie-Pathologique, Service de Chirurgie Digestive, H�pital Beaujon, Clichy, *Laboratoire d'Immunologie, H�pital Robert Debr�, Reims, France
Journal: Hepatology (1995)
High tumor necrosis factor levels are associated with exercise intolerance and neurohormonal activation in chronic heart failure patients Mariantonietta Cicoira, Aidan Bolger, Wolfram Doehner, Mathias Rauchhaus, Constantinos Davos, Rakesh Sharma, Faisal Al-Nasser, Andrew J. S. Coats, Stefan D. Anker, National Heart &amp; Lung Institute, London, United Kingdom
Journal: Journal of the American College of Cardiology (2001)
La coloscopie en France en 2006: résultats d'une enquête prospective nationale de la Société Française d'Endoscopie Digestive (SFED)
Authors: JM Canard, L Palazzo, JC Letard, JP Arpurt, J Cassigneul, P Dalbies, J Escourrou, G Gay, R Laugier, B Napoleon, T Ponchon, D Sautereau, B Richard Molard, G Tucat, B Vedrenne
Journal: Endoscopy (2008)

But: Décrire et quantifier prospectivement l'ensemble des coloscopies réalisées en France en 2006 et suivre leur évolution depuis la première enquête réalisée en 1998.
Use of Bronchoalveolar Lavage to Detect Lung Damage
Authors: Rogene F. Henderson
Journal: Environmental Health Perspectives (1984)

The assay of bronchoalveolar washings from acutely exposed animals has proven useful as a rapid screen for lung injury from inhaled airborne toxins. The screen is useful for choosing appropriate compounds and exposure levels for subsequent in-depth studies in which complete histopathologic evaluations will be made. An inflammatory response can be detected by the appearance of polymorphonuclear leukocytes and an increase in protein content of lung washings. The release of the cytoplasmic enzyme, lactate dehydrogenase, into the acellular portion of the lavage fluid serves as an indication of cell death or membrane damage. A large increase in some lysosomal enzymes has been found in the bronchoalveolar lavage fluids from animals chronically exposed to insoluble particles. Angiotensin-converting enzyme has been found to be elevated in bronchoalveolar washings from animals with endothelial cell damage in the pulmonary capillaries. The correlation of these cellular and biochemical alterations in the bronchoalveolar lavage fluid with morphological indications of damage has served to validate this method of detecting acute lung injury. Further study is needed to validate indicators of developing chronic disease.
Results of the second interim assessment of rEECur, an international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma (RR-ES).
Authors: Martin G. McCabe, Laura Kirton, Maria Khan, Nicola Fenwick, Uta Dirksen, Nathalie Gaspar, Jukka Kanerva, Thomas Kuehne, Alessandra Longhi, Roberto Luksch, Cristina Mata, Marianne Phillips, Akmal Safwat, Sandra J. Strauss, Kirsten Sundby Hall, Claudia Maria Valverde Morales, Andrew J. Westwood, Mark Winstanley, Jeremy Whelan, Keith Wheatley
Journal: Journal of Clinical Oncology (2020)

11502 Background: Five-year survival of RR-ES is about 15%. Several chemotherapy regimens are used, but without robust evidence. rEECur, the first randomised controlled trial in this setting, is defining a standard of care, balancing efficacy and toxicity. Methods: Patients aged 4 to 50 with RR-ES and fit to receive chemotherapy were randomised between topotecan &amp; cyclophosphamide (TC), irinotecan &amp; temolozomide (IT), gemcitabine &amp; docetaxel (GD) or high-dose ifosfamide (IFOS). Primary outcome measure was objective response (OR) after 4 cycles by RECIST 1.1. Secondary outcomes included PFS, OS and toxicity. A probability-based Bayesian approach was used with multiple pairwise comparisons. At the first interim analysis patients allocated to GD had worse OR and PFS than the other arms and accrual to the GD arm was halted. The second interim assessment was planned to determine which arm should be closed when at least 75 evaluable patients had been recruited to the remaining arms and evaluated for the primary outcome measure. Results: 366 patients (87% RECIST-evaluable), recruited between 18/12/14 and 17/12/19, were randomised to TC (n=124), IT (118), GD (72) and IFOS (53). Median age was 20 years (range 4-49). Patients had: refractory disease (19%), first recurrence (66%), &gt; first recurrence (14%). Initial disease site was bone in (66%). Sites of progression were: primary site only (16%) pleuropulmonary only (32%), other metastatic (52%). At median follow up of 9.2 months, outcome in the IT arm was: response rate 20%, median PFS 4.7 months (95% CI: 3.4 to 5.7), median OS 13.9 months (95% CI: 10.6 to 18.1). The table shows, for each pairwise comparison of IT with the other open arms (randomly labelled A and B to maintain blinding), the probabilities that OR, PFS and OS were better for X than for each other arm (RR = risk ratio, HR = hazard ratio). For OR, PFS and OS, all comparisons favoured arms A and B. The main grade 3/4 adverse events (% patients with an event) for IT (left hand values) compared with A and B pooled were: vomiting (6% v 1%), nausea (6% v 0%), diarrhoea (17% v 0%), fatigue (3% v 1%) and febrile neutropenia (3% v 24%). Conclusions: The first randomised trial in RR-ES has shown that IT, used as a control arm in planned and ongoing randomised phase II studies in RR-ES, is less effective than A and B in achieving tumour shrinkage or prolonging PFS and OS. The remaining two arms are continuing to recruit patients. Clinical trial information: ISRCTN36453794 . [Table: see text]
Dietary Prudence
Authors: Samuel Vaisrub
Journal: JAMA (1974)

The Golden Age of the "special diet" is over. We may still prescribe low-calorie diets for the obese, low-carbohydrate or low-fat diets for the diabetic, and salt-free diets for the hypertensive and the edematous, but our enthusiasm is at a low ebb. Not even the current vogue of the "prudent diet" for the preventions of coronary artery disease can lift us from the dietary doldrums. In some instances special diets have been reduced in importance or made unnecessary by the use of drugs and other therapies. Saluretics have spared many patients the depressing monotony of salt-free meals. Similarly, xanthine oxidase inhibitors have made it possible to relax the strictures of unpalatable low-purine diet. And dialysis has permitted a more liberal protein intake for the uremic patient. Bypassed with the aid of drugs or rendered otherwise obsolete, such diets arouse no fond nostalgic memories. Their decline causes no second thoughts. But
Levodopa aids certain movement disorders
Authors: E. R. Gonzalez
Journal: JAMA (1981)

Levodopa is finding some unorthodox neurological uses. First came reports that the agent can improve tardive dyskinesia. This was initially observed in patients who had stopped taking neuroleptic medications by Murray Alpert, PhD, professor and director of psychology, and Arnold J. Friedhoff, MD, professor and director of the Milhauser Laboratories, Department of Psychiatry, New York University School of Medicine. At a recent New York City symposium on experimental therapeutics of movement disorders, these investigators reported that levodopa also improves tardive dyskinesia in about 50% of patients who<i>continue</i>to take neuroleptics. At first the patients show worsening of their dyskinetic movements; they improve after the dopamine agonist is withdrawn. Now Ira Shoulson, MD, has found that levodopa, given in low doses, can benefit patients with coexisting residual tardive dyskinesia and residual druginduced parkinsonism. Shoulson, who is associate professor of neurology and medicine at the University of Rochester (NY) School of
BAREFOOT PLANTAR PRESSURE MEASUREMENT IN CHRONIC EXERTIONAL COMPARTMENT SYNDROME
Authors: D Roscoe, A Roberts, D Hulse, M Hughes, A Shaheen, A Bennett
Journal: British Journal of Sports Medicine (2016)

Patients with chronic exertional compartment syndrome (CECS) have pain during exercise that usually subsides at rest. Accompanying the pain, a change in gait is frequently described by patients. This typically manifests as a progressive loss of control of ankle movements, often described as ‘foot slap’. This study aimed to investigate the differences in plantar pressure between CECS cases and asymptomatic controls in a rested pre-symptomatic state. 20 men with symptoms of CECS of the anterior compartment and 20 asymptomatic controls participated. Barefoot plantar pressure was measured during walking and marching. Data was analysed to determine: stance time; foot progression angle; the mean of the medial-lateral displacement of centre of force; time from initial foot contact to initial full forefoot contact (IFFC-time); the medial-lateral distribution of pressure under the heel; and, the ratio between inner and outer metatarsal loading. Cases had shorter stance times and IFFC-times than controls. Foot progression angle was inversely related to walking speed. The area under the receiver operating curve for IFFC-time ranged from 0.746 −0.773 representing ‘fair predictive validity’. Cases have an increased rate of ankle plantarflexion after heel strike. It has recently been observed that there is almost no change in the length of the tibialis anterior muscle during the gait cycle with almost all of the changes in length of the muscle-tendon unit occurring within the tendon during walking. It follows that lowering of the foot after heel strike occurs through tendon stretch whilst the muscle contracts isometrically. Therefore if IFFC is reduced in CECS cases it is plausible that this is due to stretching of the tendon although inherent weakness in the muscle cannot be excluded. This is postulated to result from either Tibialis Anterior muscle weakness or elongation of the tendon. The observed biomechanical difference in cases may give further insight into the pathophysiology of this condition and enable further development of a non-invasive diagnostic modality. Diagnostically, the value of IFFC-time is comparable to post-exercise invasive diagnostic tests but falls short of that achieved with invasive testing during prolonged painful exercise.
Jaundice and Methyldopa
Authors: R. Wyburn-Mason
Journal: BMJ (1969)

<h3>Abstract</h3> <b>Objectives</b> To explore how general practitioners have accessed and evaluated evidence from trials on the use of statin lipid lowering drugs and incorporated this evidence into their practice. To draw out the practical implications of this study for strategies to integrate clinical evidence into general medical practice. <b>Design</b>Qualitative analysis of semistructured interviews. <b>Setting</b>General practices in Lothian. <b>Subjects</b>24&nbsp;general practitioners selected to obtain a heterogeneous sample. <b>Results</b> Respondents were generally aware of the evidence relating to the use of statins in secondary prevention of coronary heart disease, but they were less clear about the evidence in primary prevention. The benefits of statins in secondary prevention were clearer to them andthe social and economic issues less complex than was the case for use in primary prevention. Respondents rarely said they appraised the methods and content of trials, rather they judged the trustworthiness of the source of trial evidence and interpreted it within the context of the economic and social factors which impinge on their practice. Moreover, trial data become relevant for routinepractice only when underpinned by a consensus on these issues. <b>Conclusion</b> Strategies to promote incorporation of evidence from clinical trials into everyday practice are likely to be effective if they tap into and build on the process of local consensus building. Strategies such as teaching critical appraisal skills and guideline development may have little effect if they are separated from this process.
Mechanisms of Food Allergy
Authors: H. A. Sampson
Journal: Annual Review of Nutrition (1996)

Our understanding of food allergy has made tremendous strides recently. With now-relatively uniform definitions of the clinical presentations of food allergy, the scientific literature is more discernible. In this progress, we have come to understand that the prevalence of food allergy is up to 8% in children and 2% in adults. Additionally, these studies have shown the role of specific allergens and mediators in the immunopathogenesis of food allergy. Much of the information available still relates to immunoglobulin & mediated food reactions, although other immunologic mechanisms are being studied extensively. The diagnosis and treatment of food allergy is now much more standardized. Longterm studies have shown the natural history of many of these reactions.
Breast CT
Authors: Stephen J. Glick
Journal: Annual Review of Biomedical Engineering (2007)

Breast cancer is a serious disease that accounts for approximately 40,000 deaths per year in the United States. Unfortunately, there is no known cause of breast cancer, and therefore the best way to prevent mortality is early detection. In the past 15 years, breast cancer mortality has been reduced significantly, which is in part due to screening with film-screen mammography. Nonetheless, conventional mammography lacks sensitivity, especially for certain subgroups of women such as those with dense breast tissue, those under 50 years old, and pre- or perimenopausal women. In addition, mammography has a very poor positive predictive value for biopsy, with 70%-90% of biopsies performed turning out negative. By improving visualization of breast tissue, X-ray computerized tomography (CT) of the breast can potentially provide improvements in diagnostic accuracy over conventional mammography. Owing to recent technological developments in digital detector technology, flat-panel CT imagers dedicated to imaging of the breast are now feasible. A number of academic groups are currently researching dedicated breast CT and prototype systems are currently being evaluated in the clinical setting.
Redistribution of canalicular organic anion transport activity in isolated and cultured rat hepatocytes
Authors: Han Roelofsen, Conny T. M. Bakker, Berry Schoemaker, Marc Heijn, Peter L. M. Jansen, Ronald P. J. Oude Elferink
Journal: Hepatology (1995)

The hepatocanalicular transport of a large number of organic anions, such as bilirubin glucuronides and glutathione conjugates in the rat, is mediated by an adenosine triphosphate (ATP)-dependent transport system, which is termed canalicular multispecific organic anion transporter (cMOAT). This system is mainly defined by its deficiency in mutant TR − rats. We have previously reported that in cultured hepatocytes the fluorescent organic anion glutathione-bimane (GS-B) accumulates in intracellular vesicles and that this transport is mediated by cMOAT. We now show that this intracellular accumulation of fluorescent organic anion is largely absent in freshly isolated hepatocytes but appears when cells are incubated in suspension at 37°C or cultured for periods of 1 to 24 hours. The appearance of intracellular cMOAT activity coincides with the disappearance of 70% of cMOAT activity from the plasma membrane as measured by the transport activity of the cells for the organic anion dinitrophenyl-glutathione (GS-DNP). Both the appearance of intracellular cMOAT and the disappearance of transport activity from the plasma membrane were completely inhibited at temperatures below 20°C. Residual cMOAT activity in 24-hour cultured hepatocytes could be further diminished by incubation of the cells with 1 μmol/L monensin or 10 mmol/L methylamine. We conclude that after disruption of the cell polarity by collagenase isolation of the hepatocytes, remnants of apical membrane containing cMOAT are rapidly endocytosed when the cells are kept at 37°C. Evidence suggests that at least part of the transporters may recycle back to the plasma membrane after endocytosis. These observations may be relevant for the understanding of regulation of canalicular transport.