tbuckley/cabot-search huggingface dataset:
Hylan G-F 20 (Synvisc) versus placebo: Cochrane Review 2005
Authors: N. Bellamy, J. Campbell, T. Gee, V. Robinson, R. Bourne, G. Wells
Journal: Annals of the Rheumatic Diseases (2005)

Background: Osteoarthritis (OA) is the most prevalent chronic joint disorder worldwide, and is associated
with significant pain and disability. Intra-articular (IA) hyaluronan/hylan (HA) is an established local
therapeutic modality for the treatment of knee OA. The goal of therapy is to relieve the symptoms
associated with inflammation and thereby reduce pain and disability.

Objectives: As part of a Cochrane review of viscosupplementation in knee OA, randomised controlled trials (RCTs) were reviewed to evaluate evidence for the efficacy of viscosupplementation with Hylan G-F 20
compared to placebo.
Methods: Electronic searches were conducted of EMBASE, MEDLINE, PREMEDLINE, Current Contents
and CENTRAL. Human, RCTs involving Hylan G-F 20 compared to placebo, published prior to 1Q2004, were included. Trials were selected and data extracted by 2 independent reviewers. Methodological quality was assessed with the Jadad criteria by 2 reviewers. Data on OARSI core set measures were extracted. Weighted mean differences (WMD), based on unadjusted post-test scores, and 95% confidence intervals (CI) were calculated for continuous outcome measures.

Results: Seven RCTs met the inclusion criteria. Median methodological quality was 4 (range 4-5). Hylan GF
20 was more efficacious than placebo at 1-4 weeks post-injection for pain on weight-bearing WMD
(random effects [RE]) -13 mm on a 0-100 mm VAS (p=0.002) based on 6 RCTs. This difference was even
greater at 5-13 weeks post-injection, -22 mm (RE) (p=0.0006) based on 5 RCTs, and at 14-26 weeks postinjection, -21 mm (RE) (p=0.006) based on 4 RCTs. Hylan G-F 20 was more efficacious than placebo at 1-4
weeks post-injection for pain at night, WMD -7 mm on a 0-100 mm VAS (p=0.003) based on 5 RCTs. This
difference was even greater at 5-13 weeks post-injection, -11 mm (RE) (p=0.008) based on 4 RCTs, and at
14-26 weeks post-injection, -17 mm (p<0.00001) based on 3 RCTs. Hylan G-F 20 was more efficacious
than placebo at 1-4 weeks post-injection for improvement in the most painful knee movement WMD 19 mm
on a 0-100 mm VAS (p<0.00001) based on 4 RCTs. This difference was even greater at 5-13 weeks postinjection,
34 mm (RE) (p<0.00001). Hylan G-F 20 + oral placebo was more efficacious than arthrocentesis +
oral placebo for WOMAC Function, WMD -9 mm on a 0-100 mm VAS (p=0.01)and for Lequesne Index
WMD -1.60 on a 0-24 scale (p=0.02)(Dickson 2001). Hylan G-F 20 was more effective than placebo at 1-4
weeks post-injection for the variable designated treatment efficacy, WMD 22 mm on a 0-100 mm VAS
(p<0.00001) based on improvement in 4 RCTs. This difference was even greater at 5-13 weeks postinjection,
35 mm (p<0.00001).

Conclusion: Evidence from this Cochrane review supports the superior efficacy of Hylan G-F 20 compared
to placebo on weight- bearing pain, night pain, function and treatment efficacy in knee OA.
The dexamethasone suppression test in psychotic disorders
Authors: G W Arana, P J Barreira, B M Cohen, J F Lipinski, D Fogelson
Journal: American Journal of Psychiatry (1983)

Dexamethasone suppression tests were given to 69 consecutively admitted psychiatric patients. Nonsuppression rates for depression with or without melancholia and for schizophrenia were similar to those previously reported, but for mania and other psychoses the frequencies were higher than expected.
Adenylosuccinate Synthetase 1 (ADSS1) gene is deleted in lung adenocarcinoma: A potential role in metabolic stress tolerance
Authors: Joshua Miller, Daniel Blake, Christopher Herzog
Journal: Cancer Research (2008)

2727  Molecular genetic studies have implicated human chromosome 14q32 and its orthologous region on mouse chromosome 12F2 as the site of a tumor suppressor gene. We performed high density deletion mapping of these regions in lung adenocarcinomas and identified the Adenylosuccinate Synthetase 1 (ADSS1) locus as the minimal site of homozygous deletion (HD). HDs of Adss1 were detected in 6 out of 13 (46%) mouse lung adenocarcinoma cell lines, and in 4 out of 43 (9.3%) mouse primary lung adenocarcinomas. Clonal HDs included the nearest flanking genes, Siva1 and Fh2bd, in 15% and 0% of the cell lines, respectively. Also, partial deletions (PD) of Adss1, including both hemizygous and sub-clonal homozygous losses, were detected in 24 out of 43 (56%) mouse primary lung adenocarcinomas, and in 6 out of 13 of the cell lines. In human lung adenocarcinomas and cell lines ADSS1 HDs occurred in 3 out of 24 (12.5%), and PDs in 10 out of 24 (42%) cases. Again less frequent deletion of nearest neighboring genes indicated that ADSS1 was the primary target of inactivation. ADSS1 is a key enzyme in the de novo synthesis of adenosine monophosphate (AMP), an essential cellular metabolite. An elevated ratio of AMP/ATP activates the cellular system for restricting energy use and suppressing tumor growth under metabolic stress conditions, such as hypoxia. Reduced AMP levels and increased tolerance to hypoxia was observed in immortalized lung epithelial cells following ADDS1 knock-down. Conversely, restoration of ADSS1 expression in lung adenocarcinoma cell lines increased cellular AMP production and stimulated apoptosis. These results suggest that ADSS1 inactivation disrupts the AMP-dependent response to metabolic stress, which favors tumor survival and growth under otherwise prohibitive metabolic conditions.
Abstract #LB-150: A fully human anti-CXCR4 antibody induces apoptosis in vitro and shows anti tumor activity in vivo.
Authors: Michelle Kuhne, Tanya Mulvey, Blake Belanger, Sharline Chen, Chin Pan, Colin Chong, Jerry Jiang, Wafa Niekro, Tom Kempe, Karla Henning, Lewis Cohen, Diann Blanset, Alan Korman, Pina Cardarelli
Journal: Cancer Research (2009)

CXCR4 has been identified as a prognostic indicator for acute myeloid leukemia (AML) in which greater expression of CXCR4 correlates with disease severity. In the normal setting CXCR4 is predominantly expressed on B and T cells, monocytes, macrophages, NK and dendritic cells, as well as lymphoid and myeloid precursor cells. CXCR4 is a seven-transmembrane, G-protein-coupled receptor in the CXC chemokine receptor family. In response to stimulation with the chemokine CXCL12, CXCR4 activates chemotaxis and mediates directional migration of hematopoietic cells. MDX-1338 is an anti-human CXCR4-specific, fully human monoclonal antibody. In vitro studies demonstrate that MDX-1338 binds to CXCR4-expressing cells with low nanomolar affinity. MDX-1338 blocks CXCL12 ligand binding to CXCR4 expressing cells and inhibits CXCL12 induced migration and calcium flux with low nanomolar EC 50  values. MDX-1338 is an IgG 4 , and thus lacks complement dependent cytotoxicity (CDC) activity and antibody dependent cell mediated cytotoxicity (ADCC) activity. MDX-1338 induces apoptosis in a range of CXCR4 expressing cell lines and also has anti-tumor activity in multiple AML and lymphoma tumor xenograft models. In a therapeutic human Burkitt\#8217;s lymphoma model, in which Ramos cells are implanted subcutaneously, MDX-1338 inhibited tumor growth approximately 58%-78% in a dose range of 1-30 mg/kg. In two Ara-C refractory AML models, Nomo-1 and HL60, MDX-1338 induced significant tumor growth inhibition at a dose of 10 mg/kg. MDX-1338 is being developed initially for the treatment of relapsed/refractory AML and ALL. Here we demonstrate the characterization and activities of MDX-1338 in vitro and in vivo.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-150.
THE DOCTOR AS CITIZEN
Authors: H A MOE
Journal: Annals of Internal Medicine (1950)

Article1 February 1950THE DOCTOR AS CITIZENHENRY ALLEN MOEHENRY ALLEN MOESearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-32-2-309 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWhen, to fulfill the promise made in response to your president's persuasive and friendly charm, a man like me sits down at his table to consider what he may say that will be worth a half-hour of your time at the end of several busy and intellectually full days, he really has a question to answer. What can a man possibly say that many, perhaps most, among you could not say better, have not thought about more cogently? What is there of thought about "The Doctor as Citizen" that a lawyer, as I am, and an executive officer of a... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Convocation address, Thirtieth Annual Session, American College of Physicians, New York, N. Y., March 30, 1949. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byBack to the Future 1 February 1950Volume 32, Issue 2Page: 309-317 ePublished: 1 December 2008 Issue Published: 1 February 1950 PDF downloadLoading ...
Nonhepatosplenic γδ T-Cell Lymphoma: A Subset of Cytotoxic Lymphomas With Mucosal or Skin Localization
Authors: Bertrand Arnulf, Christiane Copie-Bergman, Marie-Hélène Delfau-Larue, Anne Lavergne-Slove, Jacques Bosq, Janine Wechsler, Michel Wassef, Claude Matuchansky, Bernard Epardeau, Marc Stern, Martine Bagot, Felix Reyes, Philippe Gaulard
Journal: Blood (1998)
Charlas de Café. Pensamientos, anécdotas y confidencias.
Authors: Santiago Ramón y Cajal
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 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
Abstract 15691: Endothelial ADAR1-Mediated RNA Editing Controls Cathepsin S mRNA Stability and Angiogenesis
Authors: Konstantinos Stellos, Aikaterini Gatsiou, Reinier A Boon, David John, Boris Fürtig, Yosif Manavski, Anuradha Doddaballapur, Federica F Lunella, Carolin Amrhein, Xintian You, Shizuka Uchida, Jes-Niels Boeckel, Wei Chen, Harald Schwalbe, Andreas Zeiher, Stefanie Dimmeler
Journal: Circulation (2014)

Background:  Adenosine deaminase acting on RNA-1 (ADAR1) enzyme catalyze adenosine-to-inosine (A-to-I) RNA editing in double-stranded RNA. However, the functional significance of this posttranscriptional RNA regulatory mechanism has not been reported so far in vascular system.   Methods and Results:  ADAR1 and ADAR2 are expressed on mRNA and protein level in human venous umbilical endothelial cells (HUVECs). Upon ADAR1 knockdown with short-interfering RNA, a significant reduction of angiogenic sprouting and tube formation, but not of cell viability or proliferation, was observed. Endothelial-specific inducible genetic ablation of ADAR1 in mice leads to impaired postnatal retinal angiogenesis, as revealed by significantly decreased vascular outgrowth and reduced vessel branching. Endothelial cell transcriptome sequencing revealed that ADAR1 is the main RNA editor inducing A-to-I RNA editing events. Cathepsin S (CTSS), which has an important function in angiogenesis and vascular diseases, was among the highest ADAR1 edited targets. Silencing of ADAR1 reduced CTSS mRNA and protein expression. Supplementation of spheroids with recombinant human CTSS partially rescued the ADAR1 knockdown-induced impairment of endothelial cell sprouting. In order to identify the mechanism of underlying CTSS regulation by ADAR1, we first tested the impact of RNA editing on CTSS mRNA secondary structure. With the help of NMR spectroscopy, we observed that RNA editing alters mRNA base-pairing and folding. RNA-immunoprecipitation experiments showed that silencing of ADAR1 reduced the binding of the stabilizing RNA-binding protein HuR to CTSS 3’UTR by about 80%. Luciferase reporter gene expression assays further confirmed our findings suggesting that RNA editing regulates HuR binding to AU-rich elements at CTSS 3’UTR.   Conclusions:  These results demonstrate a novel mechanism of endothelial ADAR1 and RNA editing in gene expression and vascular function.
Effect of asthma treatment on fitness, daily activity and body composition in children with asthma
Authors: S. Vahlkvist, M. D. Inman, S. Pedersen
Journal: Allergy (2010)

To cite this article: Vahlkvist S, Inman MD, Pedersen S. Effect of asthma treatment on fitness, daily activity and body composition in children with asthma. Allergy 2010; 65 : 1464–1471. Abstract Background: Although several cross‐sectional studies have assessed the daily physical activity in children with asthma, the impact of the level of asthma control remains unknown. Aim: To assess the influence of asthma treatment–induced changes in asthma control on daily physical activity, cardiovascular fitness and body composition in children with asthma. Methods: Daily accelerometer‐measured physical activity, cardiovascular fitness, body composition (percent fat, percent lean tissue and bone mineral density) and a variety of asthma outcomes (to assess the level of asthma control) were measured over 4 weeks in 55 children with newly diagnosed untreated asthma and 154 healthy, sex and age‐matched controls. Treatment with inhaled corticosteroids was initiated after the baseline period. All outcome measurements were repeated after 1 year and some also during the year of treatment. Results: Asthma control improved markedly during the year of treatment. The improvement in control was associated with a significant increase in total daily activity of 2.8 h/week compared with the healthy controls ( P &lt; 0.001). In addition, significant increases were seen in moderate‐vigorous activity (33 min/week; P = 0.01) and in cardiovascular fitness (1.2 ml O 2 /min*kg) compared with the healthy controls. The improvement in activity was mainly seen during the last 6 month of the study. No difference was seen between the two groups in changes in percent body fat. Conclusion: Poorly controlled asthma is associated with reduced physical activity and cardiovascular fitness. Improvement in asthma control is associated with a clinically relevant increase in daily physical activity and cardiovascular fitness.
MicroRNA isolation and analysis from human whole blood
Authors: Gary J. Latham, Timothy S. Davison, Jon Kemppainen
Journal: Clinical Cancer Research (2006)

A108   MicroRNAs (miRNAs) represent an exciting new class of small, regulatory biomolecules. Data to date suggests that as many as half of all genes may be regulated by miRNAs. Over the past few years, scientists have demonstrated that miRNAs play important roles in processes as diverse as early development, cell proliferation and differentiation, apoptosis and fat metabolism, and oncogenesis. Indeed, tumor-associated, differentially expressed miRNAs, termed oncomirs, have been found in more than a half dozen different cancers and the number of known oncomirs is growing rapidly.Blood is a readily accessible tissue that carries biological material from all reaches of the body, and is the preferred clinical sample for many diagnostic tests. Blood-borne cells such as lymphocytes, monocytes, neutrophils, eosinophils, and basophils contain molecular clues of infection, inflammation, and other hallmarks of disease. We hypothesize that miRNA biomarkers exist in blood, and further that these biomarkers will drive the development of future molecular diagnostics assays. However, technologies for isolating and analyzing the global miRNA profile in human whole blood are largely lacking. For example, the most widely used protocol for whole blood RNA stabilization and isolation, the PAXgene™ Blood RNA System, does not provide for the recovery of small RNA. As a result, we developed a novel methodology using PAXgene stabilized blood that enables the isolation of mature, ~21-mer miRNAs. Using microarrays, we then compared the expression levels of >380 miRNAs in blood with the miRNA profile from nearly two dozen other healthy human tissues. Outlier analysis enabled the identification of miRNAs that were relatively differentially expressed in whole blood with respect to the expression profiles from a large set of reference tissues. The implications of these findings are discussed.
Methadone treatment
Authors: J R Robertson, J Macleod
Journal: BMJ (1996)

infusion ended, an event better supervised during the normal working day.We do not agree that all patients with methadone overdose should be admitted empirically for 72 hours or that pulse oximetry should be performed continuously for this time.This would result in unnecessarily protracted admissions and inappropriate use of monitoring equipment.Pulse oximetry will not detect hypoventilation in a patient being given supplemental oxygen.'After an initial bolus, the early introduction of a naloxone infusion titrated to the clinical response is appropriate management; this can be stopped after 12-24 hours with the patient kept under close clinical scrutiny for sev- eral hours thereafter, particular attention being paid to the conscious level and respiratory rate and depth.Any deterioration in these variables necessitates resumption of the naloxone infusion with an initial bolus as required.In summary, in this case flumazenil was inappropriately given and the use of naloxone can best be described as too little, with the infusion being given too late and stopped too soon, apparently without adequate clinical supervision.The clinical toxicology results are interesting, but only in relation to the postmortem discussion.The lessons in this case are not those advanced by the authors.
Current Trends, Evaluation, and Management of Pediatric Nephrolithiasis
Authors: Joel D. Hernandez, Jonathan S. Ellison, Thomas S. Lendvay
Journal: JAMA Pediatrics (2015)

The incidence of pediatric nephrolithiasis has been steadily increasing for the past several decades, with a concomitant concerning increase in health care costs and burden to children with this disease. Recent population-based studies have also demonstrated a change in the current trends of pediatric nephrolithiasis that is characterized by a significant increase in the number of girls now being affected. While changes in diet and lifestyle, obesity prevalence, and even imaging practices have been proposed to contribute to the recent increase in pediatric nephrolithiasis, a definite underlying cause remains elusive. This situation is complicated by the fact that, unlike in adults, the trends occurring in pediatric nephrolithiasis have not been studied rigorously, which contributes to the paucity of data in children. The level of concern with the increasing incidence is raised by factors unique to pediatric nephrolithiasis that could expose an affected child to more complications. Factors such as variable clinical presentation, high recurrence of kidney stones associated with abnormalities of metabolism and the urinary tract, and the possible presence of rare genetic kidney stone diseases would require physicians to comprehensively evaluate patients presenting with kidney stones. The goal of evaluation is to identify modifiable risk factors and abnormalities for which targeted therapy can be prescribed. The goals of medical and surgical treatments are to eliminate the burden of kidney stones and prevent recurrence while simultaneously minimizing complications from interventions. Patients at high risk may benefit from a specialized kidney stone clinic staffed by a pediatric nephrologist, urologist, dietitian, and clinical nurse. Such a multidisciplinary clinic can help provide the medical and surgical support needed for patients at high risk and offer key opportunities to learn more about pediatric nephrolithiasis, thereby fueling the much-needed research in this field.
An insect gut environment reveals the induction of a new sugar-phosphate sensor system in<i>Bacillus cereus</i>
Authors: Fuping Song, Qi Peng, Julien Brillard, Didier Lereclus, Christina Nielsen-LeRoux
Journal: Gut Microbes (2013)

Bacteria survive under various conditions by sensing stimuli triggering specific adaptive physiological responses, which are often based on membrane-integrated sensors connected to a cytoplasmic regulator. Recent studies reveal that mucus glycans may act as signal molecules for two-component systems involved in intestinal colonization. Bacillus cereus, a human and insect opportunistic pathogen was used to identify bacterial factors expressed in an insect gut infection model. The screen revealed a promoter involved in the expression of a gene with so far unknown functions. A search for gut-related compounds, inducing its transcription, identified glucose-6-phosphate as an activation signal. The gene is part of a five-gene cluster, including a two-component system. Interestingly such five gene loci are conserved in the pathogenic Bacillus group as well as in various Clostridia bacteria and are with analogy to other multi-component sensor systems in enteropathogenic bacteria, such as E. coli. Thus our results provide insights into the function of two-component and auxiliary sensor systems in host-microbe interactions and opens up possible investigations of such systems in other gut associated bacteria.