tbuckley/cabot-search huggingface dataset:
Macrophage Migration Inhibitory Factor Down‐Regulates the RANKL–RANK Signaling Pathway by Activating Lyn Tyrosine Kinase in Mouse Models
Authors: Se Hwan Mun, Dongmyung Oh, Sun‐Kyeong Lee
Journal: Arthritis & Rheumatology (2014)

Macrophage migration inhibitory factor (MIF) is an important modulator of innate and adaptive immunity as well as local inflammatory responses. We previously reported that MIF down-regulated osteoclastogenesis through a mechanism that requires CD74. The aim of the current study was to examine whether MIF modulates osteoclastogenesis through Lyn phosphorylation, and whether down-regulation of RANKL-mediated signaling requires the association of CD74, CD44, and Lyn. CD74-knockout (CD74-KO), CD44-KO, and Lyn-KO mouse models were used to investigate whether Lyn requires these receptors and coreceptors. The effects of MIF on osteoclastogenesis were assessed using Western blot analysis, small interfering RNA (siRNA)-targeted down-regulation of Lyn, Lyn-KO mice, and real-time imaging of Lyn molecules to surface proteins. MIF treatment induced Lyn expression, and MIF down-regulated RANKL-induced activator protein 1 (AP-1) and the Syk/phospholipase Cγ cascade during osteoclastogenesis through activated Lyn tyrosine kinase. The results of immunoprecipitation studies revealed that MIF receptors associated with Lyn in response to MIF treatment. Studies using Lyn-specific siRNA and Lyn-KO mice confirmed our findings. Our findings indicate that the tyrosine kinase Lyn is activated when MIF binds to its receptor CD74 and its coreceptor CD44 and, in turn, down-regulates the RANKL-mediated signaling cascade by suppressing NF-ATc1 protein expression through down-regulation of AP-1 and calcium signaling components.
Invasive listeriosis in Denmark 1994–2003: a review of 299 cases with special emphasis on risk factors for mortality
Authors: P. Gerner-Smidt, S. Ethelberg, P. Schiellerup, J.J. Christensen, J. Engberg, V. Fussing, A. Jensen, C. Jensen, A.M. Petersen, B.G. Bruun
Journal: Clinical Microbiology and Infection (2005)
Addressing the issue
Authors: Neville W Goodman
Journal: BMJ (2001)

“address (v) 1 write someone's name on (envelope or parcel). 2 speak formally to, direct one's remarks to. 3 think about and begin to deal with. 4 (golf) prepare to hit (the ball).”1

Address in its third sense has joined “involve” as a “lazily overused”2 verb that “makes it the delight of those who dislike the effort of searching for the right word”3 or “the trouble of precise thought.”4 Searching bmj.com for “addresses” or “addressing” mines a rich seam. There is almost nothing that cannot be addressed: …
Abstract 14883: Atrial SERCA2a Overexpression Has No Effect on Cardiac Alternans but Promotes Arrhythmogenic SR Calcium Triggers
Authors: Michelle M Jennings, Xioaping Wan, Kenneth R Laurita, Michael J Cutler
Journal: Circulation (2014)

Background:  Atrial fibrillation (AF) is the most common arrhythmia in humans yet; treatment for AF has remained sub-optimal due to a poor understanding of the underlying mechanisms. Cardiac alternans has been found to precede AF episodes, suggesting an important arrhythmia substrate. Recently, we demonstrated that SERCA2a overexpression suppresses cardiac alternans and arrhythmias in the ventricle. Therefore, we hypothesized that SERCA2a overexpression will decrease cardiac alternans and arrhythmias in the atrium.   Methods:  Adult rat isolated atrial myocytes where divided into three treatment groups 1) Control, 2) SERCA2a overexpression (Ad.SERCA2a) and 3) SERCA2a inhibition (Thapsigargin, 1μm). Intracellular Ca 2+  was measured using Indo-1 AM  and Ca 2+  alternans (Ca-ALT) was induced with a standard ramp pacing protocol.   Results:  As predicted, SR Ca 2+  reuptake was enhanced with SERCA2a overexpression ( p   p   p = 0.73 ). In contrast, SERCA2a overexpression resulted in increased spontaneous SR Ca 2+  release events compared to inhibition and control myocytes (28%, 0% and 0%, respectively,  p   p   in vivo  atrial arrhythmia inducibility in control and Ad.SERCA2a animals using an esophageal burst atrial pacing protocol. There were no inducible atrial arrhythmias in Ad.GFP (n=4) animals though 25% of Ad.SERCA2a (n=4) animals had inducible atrial arrhythmias ( p  = 0.28).   Conclusions:  Our findings suggest that unlike the ventricle, SERCA2a is not a key regulator of cardiac alternans in the atrium. Importantly, SERCA2a overexpression in atrial myocytes can increase spontaneous SR Ca 2+  release, which may be arrhythmogenic.
An Old Woman With Cat
Authors: M. Therese Southgate
Journal: JAMA (2004)

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
Gasoline-sniffing by an adult. Report of a case with the unusual complication of lead encephalopathy
Authors: W. R. Law
Journal: JAMA (1968)

An adult chronically sniffed gasoline vapor, and lead encephalopathy developed. The diagnosis of organic lead intoxication was established in this patient, who presented clinically with a chronic psychosis. The unique complication of lead encephalopathy, with the unusually high blood lead level, is explained by the methodical and intense inhalation of partially evaporated gasoline. Recognition and treatment of lead encephalopathy is important for future cases.
201. Angiogenic Gene Therapy of Coronary Artery Disease – from Bench to the Clinic
Authors: Maciej Malecki, Piotr Kolsut, Zbigniew Religa, Przemyslaw Janik
Journal: Molecular Therapy (2004)

Angiogenesis is a multistep process that plays a crucial role in the development of vascular supply in normal tissue and it is also involved in many ischemic diseases like heart disease, peripheral vascular disease and also tumor growth and metastasis. So far, a manipulation of angiogenesis in vivo by gene therapy methods is an example of successful way of treatment in the clinic. We have constructed an expression vector encoding one of the most powerfull angiogenic factor, namely vascular endothelial growth factor (VEGF165). The pVEGF vector was successfully tested in vitro as well as on animals. Laboratory study demonstrated its safety and the unique abilities to induce new vessels formation. The biochemical parameters like chemical stability of the plasmid preparations and the microbiological purity and endotoxins contamination were also tested. Finally the pharmaceutical grade preparation of the pVEGF plasmid was used in the clinic. We initiated clinical study to determine safety and activity of the pVEGF plasmid administered directly into the myocardium as the only treatment. pVEGF was injected into 16 patients in the dose of 400 μg directly into ischaemic, viable myocardium. The ejection fraction (%EF) < 30%, fertile females, acute myocardial infarction (MI), retinopathy and neoplasms excluded patients from the study. The treated patients had no possibility of another treatment for example of CABG because of surgical limitations and the application of VEGF gene was the only solution. %EF, myocardial perfusion, ECHO, angiogram, ventriculography, quality of life and nitroglycerin consumption were evaluated pre- and postoperatively. The obtained results showed that most of the patients tolerated the treatment uneventfully. Most of patients were angina free at 6 months after surgery. Patients reported much better quality of life and reduction of nitroglycerin consumption. A reduction in ischaemic defects on SPECT scans were observed, particularly on rest SPECT scans. In some of patients angiography revealed improved collateral filling. No improvement of %EF has been noticed, so far. In summary it may be concluded that the pVEGF plasmid encoding vascular endothelial growth factor have the angiogenic potency observed in laboratory as well as in the clinic. It could be said that intramyocardial application of pVEGF is safe and well tolerated. The preliminary data revealed the improvement of clinical state of the patients.
Osteophytes, Enthesophytes, and High Bone Mass: A Bone‐Forming Triad With Potential Relevance in Osteoarthritis
Authors: Sarah A. Hardcastle, Paul Dieppe, Celia L. Gregson, Nigel K. Arden, Tim D. Spector, Deborah J. Hart, Mark H. Edwards, Elaine M. Dennison, Cyrus Cooper, Martin Williams, George Davey Smith, Jon H. Tobias
Journal: Arthritis & Rheumatology (2014)

Previous studies of skeletal remains have suggested that both enthesophytes and osteophytes are manifestations of an underlying bone-forming tendency. A greater prevalence of osteophytes has been observed among individuals with high bone mass (HBM) compared with controls. This study was undertaken to examine the possible interrelationships between bone mass, enthesophytes, and osteophytes in a population of individuals with extreme HBM.Cases of HBM (defined according to bone mineral density [BMD] Z scores on dual x-ray absorptiometry) from the UK-based HBM study were compared with a control group comprising unaffected family members and general population controls from the Chingford and Hertfordshire cohort studies. Pelvic radiographs from cases and controls were pooled and evaluated, in a blinded manner, by a single observer, who performed semiquantitative grading of the radiographs for the presence and severity of osteophytes and enthesophytes (score range 0-3 for each). Logistic regression analysis was used to identify significant associations, with a priori adjustment for age, sex, and body mass index.In this study, 226 radiographs from HBM cases and 437 radiographs from control subjects were included. Enthesophytes (grade ≥1) and moderate enthesophytes (grade ≥2) were more prevalent in HBM cases compared with controls (adjusted odds ratio [OR] 3.00 [95% confidence interval (95% CI) 1.96-4.58], P < 0.001 for any enthesophyte; adjusted OR 4.33 [95% CI 2.67-7.02], P < 0.001 for moderate enthesophytes). In the combined population of cases and controls, the enthesophyte grade was positively associated with BMD at both the total hip and lumbar spine (adjusted P for trend < 0.001). In addition, a positive association between osteophytes and enthesophytes was observed; for each unit increase in enthesophyte grade, the odds of any osteophyte being present were increased >2-fold (P < 0.001).Strong interrelationships were observed between osteophytes, enthesophytes, and HBM, which may be helpful in defining a distinct subset of patients with osteoarthritis characterized by excess bone formation.
Abstract 14666: Intensive Lifestyle Intervention Further Reduces High-Sensitivity C-Reactive Protein in Statin Users, Findings From the Look Ahead (Action for Health in Diabetes) Study
Authors: L. Maria Belalcazar, Steven M Haffner, David M Reboussin, Dawn C Schwenke, Ron C Hoogeveen, Russell P Tracy, Andrea M Kriska, F. Xavier Pi-Sunyer, Christie M Ballantyne
Journal: Circulation (2010)

Background: Both statin therapy and intensive lifestyle intervention have been shown to decrease high sensitivity C-reactive protein (hs-CRP), however it is unclear if lifestyle intervention has si...
Abstract 15989: Eighteen Year Clinical and Echocardiographic Follow up of the Freestyle Stentless Bioprostheses
Authors: Vincent Tchana-Sato, Francois Dagenais, Pierre Voisine, Jean Perron, Sandro Sponga, Daniel Doyle, Siamak Mohammadi
Journal: Circulation (2011)

Objectives: Stentless aortic bioprostheses were designed to provide enhanced hemodynamic performances and potentially greater longevity due to lower mechanical stress on the leaflets. The present r...
Abstract 3697: SIRT2 is a modulator of response to targeted therapies through regulation of MEK kinase activity
Authors: Prashanth K. Bajpe, Anirudh Prahallad, Hugo Horlings, Iris Nagtegaal, Roderick Beijersbergen, Rene Bernards
Journal: Cancer Research (2014)

Abstract Resistance to targeted therapies is a major problem in cancer treatment. The Epidermal Growth Factor Receptor (EGFR) antibody drugs are effective in a subset of colorectal cancers, but the molecular mechanisms of resistance are understood poorly. Genes involved in epigenetic regulation are frequently deregulated in cancer, raising the possibility that such genes also contribute to drug resistance. To address this question, we compiled an shRNA library for chromatin modifying enzymes, chromatin remodelers, and many other factors associated with chromatin regulation. Using this library, we performed a loss of function genetic screen in colon cancer cell lines sensitive to EGFR inhibitors. We identified SIRT2, a NAD+ dependent deacetylase, as a modulator of the response to EGFR inhibitors in colon and lung cancer. Mechanistically, loss of SIRT2 expression enhanced MEK acetylation, resulting in increased ERK activity. Conversely, overexpression of SIRT2 led to reduced phospho ERK and inhibition of growth. SIRT2 loss also conferred resistance to BRAF and MEK inhibitors in BRAF mutant melanoma and KRAS mutant colon cancers, respectively. These results warrant a further investigation into a potential role of SIRT2 in resistance to drugs that act in the Receptor Tyrosine Kinase-RAS-RAF-MEK-ERK signaling pathway. Citation Format: Prashanth K. Bajpe, Anirudh Prahallad, Hugo Horlings, Iris Nagtegaal, Roderick Beijersbergen, Rene Bernards. SIRT2 is a modulator of response to targeted therapies through regulation of MEK kinase activity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3697. doi:10.1158/1538-7445.AM2014-3697
Abstract 11401: Electrophysiological Basis for Atrial Arrhythmia in a Long QT Syndrome Mouse Model
Authors: Marc D Lemoine, Xiao Yan Qi, Denis Chartier, Larissa Fabritz, Paulus Kirchhof, Stanley Nattel
Journal: Circulation (2010)

Introduction: Long-QT syndromes (LQTSs) are known to cause ventricular tachyarrhythmias, but increasing evidence indicates they can also cause atrial fibrillation. Although atrial early afterdepolarizations (EADs) are a plausible cause, there are no published studies of cellular arrhythmia mechanisms at the atrial level in models of congenital LQTS. We therefore studied atrial-cellular electrophysiology in mice with an LQTS-3 SCN5A inactivation-impairing mutation (ΔKPQ) and matched littermate controls (WT). Methods: Late Na+ current (INaL) was measured with whole-cell patch-clamp. Transmembrane action potentials (APs) were recorded with floating microelectrodes from the epicardial side of the isolated left atrium, paced at 6 frequencies between 0.5 and 10 Hz, at 35°C (pH 7.4). Ranolazine (10 μM) was used as an INaL-blocker. Results: As expected, INaL was increased in atrial myocytes of ΔKPQ mice (Figure A). APs in ΔKPQ-mice were significantly prolonged over all frequencies. AP-duration (APD) prolongation ...
Association of wheezing phenotypes in the first 7 years of life with fractional exhaled nitric oxide and lung function in adolescence. The ALSPAC study
Authors: Liesbeth Duijts, Raquel Granell, Jonathan A.C. Sterne, John A. Henderson
Journal: European Respiratory Journal (2011)

Background:  Patterns of wheezing during early childhood are associated with lung function and bronchial hyperresponsiveness in mid childhood. Little is known about the associations of early wheezing phenotypes with fraction of exhaled nitric oxide (FeNO), a marker of allergic airway inflammation, and lung function in adolescence.   Methods:  This study was based on 6,841 children in a population-based prospective birth-cohort study. Latent class analysis identified 6 wheezing phenotypes (never/infrequent, transient early, prolonged early, intermediate, late, persistent) based on wheezing patterns from birth to 7 years. FeNO levels and airway function (forced expiratory volume in 1 s (FEV1), forced expiratory volume in 1 s/forced expiratory volume ratio (FEV1/FVC), mid forced expiratory flow (FEF25-75)) were measured at age 15.   Results:  Intermediate onset wheezing (18 months) was the most strongly associated with increased FeNO levels (ratio geometric means 2.01, 95% confidence interval: (1.63, 2.48)), compared with the reference group never/infrequent wheezing. Wheezing phenotypes were not associated with FEV1, but showed associations with decreased levels of FEV1/FVC and FEF25-75 (most strongly for persistent wheezing: mean differences -0.50 (-0.62, -0.38) and -0.42 (-0.54, -0.29), respectively).   Conclusions:  Wheezing phenotypes with onset after the age of 18 months and persistent wheezing were the most strongly associated with FeNO levels and lung function, respectively, in adolescence. Our results suggest that specific patterns of asthma-related symptoms in early life are associated with markers of lung morbidity at older ages.
Multiple lipomatosis in a patient with familial atypical mole syndrome
Authors: None Tsao, None Sober
Journal: British Journal of Dermatology (1998)

Journal Article Multiple lipomatosis in a patient with familial atypical mole syndrome Get access H. Tsao, H. Tsao Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, U.S.A. E‐mail: tsao.hensin@mgh.harvard.edu Search for other works by this author on: Oxford Academic Google Scholar A.J. Sober A.J. Sober Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, U.S.A. E‐mail: tsao.hensin@mgh.harvard.edu Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 139, Issue 6, 1 December 1998, Pages 1118–1119, https://doi.org/10.1046/j.1365-2133.1998.2576g.x Published: 01 December 1998
The purinergic receptor P2Y<sub>2</sub> receptor mediates chemotaxis of dendritic cells and eosinophils in allergic lung inflammation
Authors: T. Müller, B. Robaye, R. P. Vieira, D. Ferrari, M. Grimm, T. Jakob, S. F. Martin, F. Di Virgilio, J.‐M. Boeynaems, J. C. Virchow, M. Idzko
Journal: Allergy (2010)

To cite this article: Müller T, Robaye B, Vieira RP, Ferrari D, Grimm M, Jakob T, Martin SF, Di Virgilio F, Boeynaems J‐M, Virchow JC, Idzko M. The purinergic receptor P2Y 2 receptor mediates chemotaxis of dendritic cells and eosinophils in allergic lung inflammation. Allergy 2010; 65 : 1545–1553. Abstract Background: Extracellular ATP contributes to the pathogenesis of asthma via signalling at purinergic receptors. However, the precise purinergic receptors subtypes mediating the pro‐asthmatic effects of ATP have not been identified, yet. Methods: In vivo studies were performed using the OVA‐alum model. Functional expression of the P2Y 2 purinergic receptor subtype on human monocyte‐derived dendritic cells and eosinophils was investigated using real‐time PCR, migration assays, and production of reactive oxygen species. Results: Compared to wild‐type animals P2Y 2 −/− mice showed reduced allergic airway inflammation which can be explained by defective migration of blood myeloid DCs towards ATP in vitro and in vivo , whereas the influence of ATP on maturation and cytokine production was not changed. Additionally, ATP failed to induce migration of bone marrow–derived eosinophils from P2Y 2 R‐deficient animals. The relevance of our findings for humans was confirmed in functional studies with human monocyte‐derived DCs and eosinophils. Interestingly, stimulation of human DCs derived from allergic individuals with house dust mite allergen induced functional up‐regulation of the P2Y 2 R subtype. Furthermore, eosinophils isolated from asthmatic individuals expressed higher levels of P2Y 2 R compared to healthy controls. This was of functional relevance as these eosinophils were more sensitive to ATP‐induced migration and production of reactive oxygen metabolites. Conclusions: In summary, P2Y 2 R appears to be involved in asthmatic airway inflammation by mediating ATP‐triggered migration of mDCs and eosinophils, as well as reactive oxygen species production. Together our data suggest that targeting P2Y 2 R might be a therapeutic option for the treatment of asthma.
Allergy must also be a factor
Authors: T. A E Platts-Mills, G. P Rakes, P. W Heymann
Journal: BMJ (1995)

problem of stratification and selection for admission to those units.Finally, it is worth emphasising that not all investigations are of unproved value and that effective strategies for managing high risk patients do exist.We can avoid surgery altogether, and, indeed, quantification of risk may be particularly important in those operations, such as carotid endarterectomy, in which the benefit of surgery disappears at a given (and low) rate of perioperative complications.'As we stated in our last paragraph, further studies are urgently needed; these should not only assess methods of stratifying risk but also evaluate their effectiveness in reducing morbidity.Until such evidence is forthcoming, our article sum- marises the best methods available.
Drug points: Interaction between warfarin and topical miconazole cream
Authors: A Devaraj
Journal: BMJ (2002)

diagnosis and treatment of mental illnesses.A substantial proportion of young people who commit suicide may have an untreated, under treated, or undiagnosed mental illness.The rate of suicide was even greater in females admitted with a mental illness, confirmed by a recent study of suicide in adults. 21The most likely explanation for this is that young males, not treated for mental illness had a higher suicide rate than their female counterparts.Furthermore, the rate is strongly linked to disorders that are more common among females; in our study all but schizophrenia. 22e found that mental illness in young people and a family history of suicide and mental illness were the most important risk factors for suicide among young people.Therefore an important target in the prevention of suicide in young people would be the early recognition and treatment of mental illness.Improved psychopathological assessment and treatment after discharge from psychiatric facilities could therefore help decrease suicide rates.However, as only 30% of the suicides in our study could be attributed to these factors, preventive measures should be aimed at the general population.