tbuckley/cabot-search huggingface dataset:
Internet-Based Continuing Medical Education
Authors: David A. Cook
Journal: JAMA (2006)

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
Body dysmorphic disorder in patients with anxiety disorders and major depression: a comorbidity study
Authors: O Brawman-Mintzer, R B Lydiard, K A Phillips, A Morton, V Czepowicz, N Emmanuel, G Villareal, M Johnson, J C Ballenger
Journal: American Journal of Psychiatry (1995)

The authors evaluated the frequency of body dysmorphic disorder in patients with a primary diagnosis of anxiety disorders and major depression.Patients with social phobia (N = 54), obsessive-compulsive disorder (N = 53), generalized anxiety disorder (N = 32), panic disorder (N = 47), and major depression (N = 42) and normal comparison subjects (N = 33) were studied.Body dysmorphic disorder was most common in patients with social phobia (11%) and obsessive-compulsive disorder (8%); it was less prevalent among patients with panic disorder (2%), generalized anxiety disorder (0%), and major depression (0%) and among normal subjects (0%).These findings suggest that body dysmorphic disorder may share etiologic elements with social phobia and obsessive-compulsive disorder.
Isozyme-selective activity of the HDAC inhibitor MS-275.
Authors: Takayuki Tatamiya, Akiko Saito, Tatsuo Sugawara, Osamu Nakanishi
Journal: Cancer Research (2004)

2451  The inhibitors of histone deacetylase (HDAC) have potential as a new class of antitumor agents. So far, 18 HDACs have been identified and classified into 3 classes, Class I (HDACs 1, 2, 3, 8 and 11), Class II (HDACs 4, 5, 6, 7, 9 and 10) and Class III (SIRTs 1, 2, 3, 4, 5, 6 and 7). Although several classes of HDAC inhibitors such as short chain fatty acids, hydroxamic acids, cyclic peptides and benzamides have been reported, detailed analysis on isozyme selectivity has not been reported. MS-275 is an orally active benzamide compound with antitumor activity in vivo. In this study, we examined in vitro the isozyme spectrum of MS-275 in comparison with trichostatin A (TSA) and sodium butyrate (NaBu) by using recombinant human isozyme proteins, HDACs 1, 3, 4, 6, 8 and 10 and SIRT1. MS-275 strongly inhibited HDACs 1 and 3 (IC50values were 0.51 μM and 1.7 μM, respectively) compared with other HDACs (IC50values of HDACs 4, 6, 8 and 10 were >100 μM, >100 μM, 82.5 μM and 94.7 μM, respectively). On the other hand, TSA and NaBu showed different spectra in comparison to MS-275. TSA inhibited Class II isozymes as well as Class I isozymes at around nanomolar concentrations (IC50values of HDAC1, 3, 4, 6 and 10 were 4.99 nM, 5.21 nM, 27.6 nM, 16.4 nM and 24.3 nM, respectively), except HDAC8 (IC50 value was 486 nM) that needed a much higher concentration for the inhibition than the others. NaBu inhibited Class I enzymes including HDAC8 at sub-millimolar concentrations (IC50values of HDACs 1, 3 and 8 were 0.351 mM, 0.916 mM and 0.284 mM, respectively) and HDACs 4 and 10 at millimolar concentrations (IC50values were 3.10 mM and 3.14 mM, respectively), although much higher concentrations were needed to inhibit HDAC6 (IC50 value was 79.5 mM). The Class III enzyme SIRT1 was not inhibited by any of the 3 HDAC inhibitors. The finding that TSA, but neither NaBu nor MS-275, inhibited HDAC6 was consistent with the result showing that only TSA induced α-tubulin acetylation, for which inhibition of HDAC6 is needed. These results suggest that MS-275 is selective to structurally close subfamily members of Class I enzymes, HDAC1 and HDAC3, which are considered to be most important for tumor cell cycling and proliferation, whereas TSA and NaBu demonstrated broader spectra spread to Class I and Class II isozymes.
Abstract 829: Pharmacological and Genetic Evidence that GPR109a Mediates Both the Anti-lipolytic and Skin Flushing Effects of Nicotinic Acid
Authors: Samuel Hellings, Mujing Yan, Paul Sleph, David Harden, Charles Pictroski, Robert Schulingkamp, Denise Grimm, Kevin J FitzGerald, James Sutton, Bala Krishnan, Michael Lawrence, Angela Cacace, David A Gordon
Journal: Circulation (2006)
Phlebotomy to Reduce Iron Overload in Patients Cured of Thalassemia by Bone Marrow Transplantation
Authors: Emanuele Angelucci, Pietro Muretto, Guido Lucarelli, Marta Ripalti, Donatella Baronciani, Buket Erer, Maria Galimberti, Claudio Giardini, Djavid Gaziev, Paola Polchi
Journal: Blood (1997)
The effect of aqueous cream BP on the skin barrier in volunteers with a previous history of atopic dermatitis
Authors: S.G. Danby, T. Al-Enezi, A. Sultan, J. Chittock, K. Kennedy, M.J. Cork
Journal: British Journal of Dermatology (2011)

The emollient aqueous cream BP is frequently used for the treatment of atopic dermatitis (AD), yet it is associated with a high rate of adverse cutaneous reactions. It contains the harsh anionic surfactant sodium lauryl sulphate, a known negative environmental factor associated with the exacerbation of AD.To investigate the effect of aqueous cream BP on stratum corneum (SC) integrity and skin barrier function in volunteers with a predisposition to a defective skin barrier.Thirteen volunteers with a previous history of AD (no symptoms for 6 months) applied aqueous cream BP twice daily to the volar side of one forearm for 4 weeks. The other forearm was left untreated as a control. Permeability barrier function and SC integrity were determined before and after treatment by measuring transepidermal water loss (TEWL) in conjunction with tape-stripping. For comparison, 13 volunteers with current AD were recruited for assessment, without treatment, of SC integrity and skin barrier function at unaffected sites.Topical application of aqueous cream BP resulted in significant elevation of baseline TEWL and a concomitant decrease in SC integrity. Measurements made after no treatment in volunteers with current AD, at unaffected sites, suggest that application of aqueous cream BP negatively affects the skin barrier towards the damaged state associated with onset of flares of the disease.Aqueous cream BP used as a leave-on emollient caused severe damage to the skin barrier in volunteers with a previous history of AD. Aqueous cream BP should not be used as a leave-on emollient in patients with AD.
165. Long-Term Factor VIII Expression and Phenotypic Correction in a Murine Model of Hemophilia A Achieved by Immunosuppression and Non-Viral Gene Transfer Using the Sleeping Beauty Transposon
Authors: John R. Ohlfest, Scott Perkinson, Paul Lobitz, Joel Frandsen, R. Scott McIvor, Perry Hackett, Karl Clark, Jeff Essner, Nigel Key, David A. Largaespada
Journal: Molecular Therapy (2004)

Hemophilia A is an X-linked recessive genetic disorder that is characterized by sustained bleeding after trauma or injury. Currently, patients are treated by self-administration of recombinant factor VIII protein (FVIII), but this treatment is expensive and cumbersome. Gene therapy using viral vectors has been successfully used to correct the bleeding disorder in FVIII deficient mice and dogs. However, anti-viral immune responses, problems with scale-up, and insertional mutagenesis, due to a predilection for most integrating viruses to insert near genes, all raise safety and practicality questions for viral vectors. Therefore we used the Sleeping Beauty (SB) transposon system, which is delivered as plasmid DNA, to integrate a B-domain deleted FVIII genes into the chromosomes of C57BL/6J-F8−/− mice and correct the phenotype. The transposon plasmid was co-delivered with a Ubiquitin 3 promoter-regulated SB 10 transposase expression plasmid using the “hydrodynamic” method. Plasma FVIII levels were assayed in treated mice by ELISA, COAT test, and APTT clotting assay. Long-term FVIII expression (>9 weeks at present) required delivery of 280 micrograms of plasmid DNA, co-delivery of Ub-SB10 plasmid, and immunosuppression by bi-monthly 150 mg/kg cyclophosphamide injections or immunotolerization by FVIII (RefactoTM) injection in C57BL/6J-F8−/− neonates. Without immunosupression or tolerization, anti-FVIII antibody was detected in treated mice using the Bethesda assay. Transposon excision products were detected in DNA extracted from the liver of mice treated with transposon and transposase, providing evidence for transposition. Transposon insertion site analyses in hepatocytes from treated mice are ongoing. The SB transposon system thus provides non-viral means for obtaining stable FVIII gene insertion and expression for the treatment of hemophilia A.
Abstract 14639: Incremental Prognostic Utility of Brain Natriuretic Peptide and Left Ventricular Global Longitudinal Strain in Patients with Significant Aortic Stenosis
Authors: Andrew Goodman, Kenya Kusunose, Zoran B Popovic, Roosha Parikh, Tyler Barr, Richard A Grimm, Joseph F Sabik, Leonardo Rodriguez, Lars G Svensson, Brian P Griffin, Milind Y Desai
Journal: Circulation (2014)

Background:  We sought to determine the incremental prognostic utility of brain natriuretic peptide (BNP) & left ventricular global longitudinal strain (LV-GLS) in patients with moderate-severe & severe aortic stenosis (AS) & preserved LV ejection fraction (LVEF).   Methods:  We studied 531 AS patients between 1/07-12/08 with aortic valve area (AVA)    Results:  Mean Euroscore, glomerular filtration rate (GFR) & median BNP were 8±3, 73±35 ml/min/1.73 m2 & 141 [60-313] pg/ml; while 78% were in New York Heart Association Class (NYHA) ≥II. Mean LV-stroke volume index & LV-GLS were 39±10 ml/m2 & -13.9±3 %. At 4.7 ± 2 years, 405 patients (76%) underwent aortic valve replacement (AVR) & there were 131 deaths (30%). On multivariable survival analysis, age (Hazard ratio or HR 1.46), NYHA class (HR 1.27), coronary artery disease (HR 1.72), decreasing GFR (HR 1.15), increasing BNP (HR 1.16), worsening LV-GLS (HR 1.13) & AVR (time dependent covariate analysis) (HR 0.34) were independent predictors of survival. Results of net reclassification improvement (NRI) are shown in Figure 1. Kaplan-Meier curves of NYHA class vs BNP &/or LV-GLS & AVR vs BNP &/or LV-GLS are shown in Figures 2a-b.   Conclusions:  In patients with significant AS & preserved LVEF, BNP & LV-GLS independently predict mortality, providing improved risk classification, independent of clinical & echo variables. Assessment of LV-GLS & BNP improves risk stratification of AS patients with a preserved LVEF, especially asymptomatic or deemed at a low risk.
Clinically manifest X-linked recessive ichthyosis in a female due to a homozygous interstitial 1·6-Mb deletion of Xp22.31
Authors: I.F. Nagtzaam, A.P.A. Stegmann, P.M. Steijlen, J. Herbergs, J.A. Van Lent-Albrechts, M. Van Geel, M.A.M. Van Steensel
Journal: British Journal of Dermatology (2011)
Is recurrent plantar hidradenitis in children induced by exposure to a wet and cold milieu?
Authors: L. Weigl, B. Eberlein-KÖnig, J. Ring, D. Abeck
Journal: British Journal of Dermatology (2000)

Journal Article Is recurrent plantar hidradenitis in children induced by exposure to a wet and cold milieu? Get access L. Weigl, L. Weigl Department of Dermatology and Allergy, Biederstein, Technical University Munich, Biedersteiner Strasse 29, 80802 Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar B. Eberlein‐KÖnig, B. Eberlein‐KÖnig Department of Dermatology and Allergy, Biederstein, Technical University Munich, Biedersteiner Strasse 29, 80802 Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar J. Ring, J. Ring Department of Dermatology and Allergy, Biederstein, Technical University Munich, Biedersteiner Strasse 29, 80802 Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar D. Abeck D. Abeck Department of Dermatology and Allergy, Biederstein, Technical University Munich, Biedersteiner Strasse 29, 80802 Munich, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 5, 1 May 2000, Pages 1048–1050, https://doi.org/10.1046/j.1365-2133.2000.03497.x Published: 01 May 2000
Abstract 3773: Identification of ALDH1A3 as a driver of resistance to both low-dose metronomic and conventional cyclophosphamide chemotherapy in prostate cancer
Authors: Van C. Hoang, Annabelle Chow, Amy Wong, Lavarnan Sivanathan, Urban Emmenegger
Journal: Cancer Research (2014)

Abstract Prostate cancer (PCa) is the most common cancer in North American males. Conventional, maximum tolerated dose (MTD) chemotherapy with cyclophosphamide (CPA) has been used in the past for PCa treatment, but has been replaced by docetaxel. However, renewed interest in CPA is emerging given its frequent use in low-dose metronomic (LDM) chemotherapy regimens known for their antiangiogenic properties. While therapeutic resistance limits the clinical utility of both LDM and MTD CPA, such resistance appears to occur through at least partially distinct mechanisms. To investigate the molecular changes contributing to resistance formation, we have generated LDM and MTD CPA resistant PC-3 human prostate cancer cell variants (LCR and MCR, respectively), and corresponding control variants (NS), through in vivo passaging in mice. Using next-generation sequencing and gene expression analysis, we observed 453 differentially regulated genes in LCR vs NS, and 1141 genes in MCR vs NS. An intersecting set of 158 genes found to be differentially expressed in both resistant tumor cell lines was further characterized. The genes most up-regulated (including ALDH1A3, MAGEA2 and ELOVL2) and down-regulated (comprising FN1, IL8 and IGFBP3) were chosen for validation by qRT-PCR studies. We also undertook pathway analysis using the DAVID database and the Reactome FI Cytoscape Plugin. Collectively, our studies revealed that glycolysis/gluconeogenesis, biosynthesis of unsaturated fatty acids and activated drug metabolism may contribute to resistance to both LDM and MTD CPA. In addition, numerous chemokine signaling pathway-related genes were found to be downregulated. Current studies are focusing on the role of ALDH1A3 in LDM and MTD CPA resistance. ALDH1A3 is amongst the most differentially regulated genes found in our analysis, and it has been associated with chemotherapy resistance, ‘stemness’ and aggressive tumor behaviour. Despite different mechanisms of action, there are overlapping mechanisms of resistance to LDM and MTD CPA chemotherapy. If our studies confirm an essential role of ALDH13A in such resistance, this could be rapidly clinically translated by repurposing approved pharmacological ALDH inhibitors as anticancer agents. Citation Format: Van C. Hoang, Annabelle Chow, Amy Wong, Lavarnan Sivanathan, Urban Emmenegger. Identification of ALDH1A3 as a driver of resistance to both low-dose metronomic and conventional cyclophosphamide chemotherapy in prostate cancer. [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 3773. doi:10.1158/1538-7445.AM2014-3773
Decoding Darkness: The Search for the Genetic Causes of Alzheimer's Disease
Authors: Nigel Lester
Journal: BMJ (2001)

Rudolph E Tanzi, Ann B Parson 

Perseus Publishing, £18.99, pp 320 

ISBN 0 7382 0195 2 

Rating: ![Graphic][1] ![Graphic][2] 

D ecoding Darkness is something of a heart warming tale of the early years of genetic research—a time when all you needed was a good idea, a few Petri dishes, and the tenacity to spend month after month engaged in thankless and repetitive activity: cleave, zap, blot, probe ad infinitum.

The story is a chronological account of the work that led to one of the most important early …

 [1]: /embed/inline-graphic-1.gif
 [2]: /embed/inline-graphic-2.gif
All policies should be assessed for effect on health
Authors: Linda Beecham
Journal: BMJ (1998)

The BMA has called for all major policies to be assessed in advance to see whether they will benefit people's health or have unintended consequences.

The public health green paper for England, Our Healthier Nation , committed the government to introducing health impact assessment (HIA) but did not say how planners should go about it or how it should be enforced. In a new report, Health and Environmental Impact Assessment , the BMA proposes a series …
Biochemical Studies of Resistance to 6-Thioguanine
Authors: D. B. Ellis, G. A. LePage
Journal: Cancer Research (1963)

Summary  Several 6-thioguanine (TG)-resistant mouse ascites tumor were developed to facilitate the study of possible mechanisms of resistance to this drug. A comparison was made of various aspects of purine metabolism in cells of the parent tumor lines and the resistant sublines. It was confirmed that susceptible cells incorporate significant amounts of TG into their nucleic acids, whereas cells of the resistant sublines incorporate only minor amounts of TG under the same conditions. An in vitro assay for synthesis of thioguanylic acid by the nucleotide pyrophosphorylase reaction in soluble enzyme preparations was developed.  Two TG-resistant Ehrlich ascites cell sublines were developed, one of which retained its capacity for pyrophosphorylase synthesis of thioguanylic acid and one of which had a greatly decreased capacity. The first of these resistant sublines responded to combination therapy of azaserine plus TG. Azaserine pretreatment also greatly increased the quantity of thioguanylic acid formed and the amount of TG found in the nucleic acid fraction of the cells of this subline. The second TG-resistant subline failed to respond to combination therapy; similarly, azaserine pretreatment had no effect on the metabolism of TG by this line of cells. These findings support the hypothesis that the mechanisms of resistance to a given drug vary and depend upon such features of the experimental approach as the selection pressures used in selecting the resistant populations.
Lesson of the Week: Infected right atrial thrombus presenting as pulmonary embolism complicating central venous cannulation
Authors: A Sajjad, P A Carey, I R Arnold, S R Smith
Journal: BMJ (1995)

Although the vast majority of pulmonary emboli arise from the iliac and femoral veins, we present a case that illustrates that other potential sources should be considered, especially when recurrent pulmonary emboli occur despite adequate anticoagulation.

A 64 year old man presented with fever and left sided pleuritic chest pain two weeks after a laminectomy. A ventilation perfusion scan showed multiple areas of ventilation-perfusion mismatch and he was anticoagulated. Subsequently he remained well until readmission four months later with sudden onset of chest pain, dyspnoea, fever, and rigors. A pansystolic murmur was noted on examination. …
Crime of the Heart
Authors: Arthur Ginsberg
Journal: JAMA (2000)

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
Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo
Authors: Santiago Partida-Sánchez, Debra A. Cockayne, Simon Monard, Elaine L. Jacobson, Norman Oppenheimer, Beth Garvy, Kim Kusser, Stephen Goodrich, Maureen Howard, Allen Harmsen, Troy D. Randall, Frances E. Lund
Journal: Nature Medicine (2001)
Abstract 1463: Long non-coding RNA RoR and microRNA-145 regulate tumor cell invasion in triple-negative breast cancer via targeting of ADP-ribosylation factor 6
Authors: Gabriel L. Eades, Qun Zhou
Journal: Cancer Research (2014)

Abstract Triple-negative (ER-, HER2-, PR-) breast cancer (TNBC) is an aggressive disease with a poor prognosis. Currently, there is no available molecularly targeted therapy for TNBC. MicroRNA-145 (miR-145) silencing was identified as a defining marker of TNBC by molecular profiling using deep sequencing. Previous reports indicate that miR-145 may function as a growth suppressor in some breast cancers. However, we find that in TNBC miR-145 does not regulate proliferation or apoptosis but instead, miR-145 regulates tumor cell invasion. Since metastatic breast cancer remains an incurable disease we investigated miR-145 regulated pathways to identify new potential biomarkers or therapeutic targets. Here we identify a novel target of miR-145, the small GTPase ADP-ribosylation factor 6 (Arf6). We find that ARF6, a known regulator of breast tumor cell invasion, is dramatically upregulated in triple-negative and metastatic breast tumors. We find that ARF6 can regulate E-cadherin localization and impact cell-cell adhesion. Finally, we examined the molecular mechanism behind miR-145 down-regulation in TNBC. We find that when compared to ER+ disease, TNBC shows dramatic downregulation of mature miR-145, but not pri-miR-145 or pre-miR-145, indicating that loss of miR-145 is occurring post-transcriptionally and following Drosha and Dicer processing. We find that overexpression of the long non-coding RNA, lincRNA-ROR, functions as a competitive endogenous RNA sponge in TNBC. We find that lincRNA-ROR is dramatically upregulated in TNBC and in metastatic disease. Finally, we find that knockdown of lincRNA-ROR restores miR-145 expression and reduces breast tumor cell invasion. These results reveal a lincRNA-ROR / miR-145 / ARF6 pathway that is a critical regulator of invasion in TNBCs. Citation Format: Gabriel L. Eades, Qun Zhou. Long non-coding RNA RoR and microRNA-145 regulate tumor cell invasion in triple-negative breast cancer via targeting of ADP-ribosylation factor 6. [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 1463. doi:10.1158/1538-7445.AM2014-1463