tbuckley/cabot-search huggingface dataset:
THU0008 Hypermethylation of Treg-Specific Demethylated Regions in the Ikaros Transcription Factor Family Members, Helios and EOS, in Rheumatoid Arthritis Tregs
Authors: A. Skapenko, S. Lukas, S. Haupt, V. Söntgerath, J. Leipe, H. Schulze–Koops
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Members of the Ikaros family of transcription factors have been implicated in controlling the characteristic phenotype of regulatory T cells (Tregs). Ikaros family zinc finger 4 (IKZF4, Eos) mediates Foxp3-dependent gene silencing and is required to maintain the phenotype of Foxp3-positive Tregs, whereas IKFZ2 (Helios) is involved in the suppression of IL2 gene transcription and upregulation of Foxp3. An important regulation level of tissue-specific gene-expression is DNA methylation. In particular, Treg-specific gene expression is controlled by DNA methylation within characteristic clusters, <i>Treg-specific demethylation regions</i>. <h3>Objectives</h3> To analyze the DNA methylation status of Treg-specific demethylated regions of Helios and Eos in T cells from patients with rheumatoid arthritis (RA) and to compare the level of methylation to that in T cells from healthy controls. <h3>Methods</h3> In both genes, DNA methylation was assessed by bisulfite sequencing in a CpG island located in an intragenic conserved non-coding sequence (CNS). In addition, a CpG-rich region in exon 6 of the Helios gene was also analyzed. <h3>Results</h3> All analyzed regions were completely methylated in effector T cells from RA patients and controls. In contrast, considerable degrees of demethylation were detected in the regions of interest in CD25+CD127- T cells, in line with the hypothesis of an important regulatory mechanism facilitating Treg-specific gene expression. Importantly, the methylation rate of the CNS CpG island in the Helios gene was significantly higher in Tregs from RA patients than in those from controls (55% vs. 40%, p&lt;0.05). Similarly, the CpGs within exon 6 of the Helios gene were demethylated to a significantly different level between RA patients and controls (50% vs. 40% methylation, respectively; p&lt;0.05). Finally, in the CNS CpG island of the Eos gene, the methylation level in Tregs from RA patients was also significantly higher as compared to healthy control Tregs (68% vs. 53%, p&lt;0.01). <h3>Conclusions</h3> The data are consistent with the hypothesis of Treg specific expression of Helios and Eos regulated by DNA methylation within Treg-specific demethylation regions. Furthermore, the data suggest that impaired function Tregs in RA might be related to an altered expression of Helios and Eos as a consequence of increased DNA methylation. This mechanism might provide a molecular epigenetic insight into the pathogenesis of autoimmune diseases. <h3>Disclosure of Interest</h3> None declared
The Use of Perforated Cellophane for the Growth of Cells in Tissue Culture
Authors: Virginia J. Evans, Wilton R. Earle, Edward L. Schilling, Elizabeth P. Wilson, Emily Duchesne
Journal: JNCI Journal of the National Cancer Institute (1947)

The Use of Perforated Cellophane for the Growth of Cells in Tissue Culture Get access Virginia J. Evans, Virginia J. Evans cytologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Wilton R. Earle, Wilton R. Earle principal cytologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Edward L. Schilling, Edward L. Schilling technologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth P. Wilson, Elizabeth P. Wilson junior cytologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Emily Duchesne Emily Duchesne junior cytologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 8, Issue 3, December 1947, Pages 103–119, https://doi.org/10.1093/jnci/8.3.103 Published: 01 December 1947 Article history Received: 13 October 1947 Published: 01 December 1947
STEM-20MAPPING DYNAMICS OF CELL DIVISION AND GENE EXPRESSION AT THE SINGLE CELL LEVEL TO UNDERSTAND GLIOMA CELL STATES
Authors: Peter Tonge, Sameer Agnihotri, Mira Li, Julie Metcalf, Mark Bernstein, Gelareh Zadeh, Kenneth Aldape
Journal: Neuro-Oncology (2015)

GBM tumors are recognized as being heterogeneous in nature, consisting of many different cell types and cell states. This presents a major hurdle during the treatment of tumors as radiation and chemotherapeutic agents preferentially target proliferative cells. Notably, quiescent and slowly-dividing cancer stem cells are thought to provide a reserve of cells that drive cancer relapse following treatment, making them more malignant than their rapidly dividing counter-parts. To determine whether quiescent and slow dividing stem cells are a common feature within patient GBMs we profiled the dynamics of cell proliferation. GBM tumors surgically resected from patients were used to generate Patient Derived Xenograft (PDX) models in NOD SCID mice. During the two months that it takes for xenografts to establish, mice were feed with regimes of thymidine analogues (BrdU, CldU or IdU) in their drinking water, effectively tagging dividing cells, to profile the history of each glioma cell. Adapting the regimes that mice were feed thymidine analogues facilitated the characterization of cancer cell proliferation. We observe diverse proliferation dynamics within each PDX mouse, representing rapidly dividing, slowly dividing and quiescent cells. To then establish a single cell gene expression map of proliferating versus non-proliferating glioma cell states we have generated a custom Glioma Specific Epigenetic Expression (GSEE) qPCR array. The GSEE qPCR array has been utilized for the analysis of gene expression at the single cell level in patient derived glioma cells. We have subsequently generated a core network of epigenetic modifier genes that reliably represent glioma cell state. This has enabled the mapping of glioma cell states with respect to dynamics of cell division, revealing novel therapeutic targets.
Fibre Endoscopic Insertion of Palliative Oesophageal Tubes with the Nottingham Introducer<sup>1</sup>
Authors: J D R Rose, P M Smith
Journal: Journal of the Royal Society of Medicine (1983)

Using the Nottingham introducer and diazepam sedation, 93 of 100 patients with oesophagogastric malignancy have been successfully intubated, 67 with Celestin tubes and 26 with Atkinson tubes. Their mean age was 72 years (range 36-91). Six of the failures were in patients with fundal adenocarcinoma. Sixty-nine patients were discharged from hospital after initial intubation (74%). Nine patients developed a perforation, 6 died and there were 5 deaths from aspiration. Nine patients are alive up to 11 months later. The mean survival after discharge was four months with a maximum of 18 months. Later 11 tubes obstructed and 12 Celestin tubes displaced upward. Endoscopic insertion of oesophageal prosthetic tubes provides satisfactory palliation for inoperable oesophagogastric malignancy. The development of the Atkinson tube with a distal flange has eliminated tube displacement upwards.
PWE-207 Predictors of survival following percutaneous transhepatic biliary drainage
Authors: C Peplow, A King, A Nurhussein, N Ghandhi, A Ganeshan, M Mottershead, P Wilson
Journal: Gut (2015)

<h3>Introduction</h3> Percutaneous transhepatic cholangiography and biliary drainage (PTC) is an effective therapeutic intervention in the management of benign and malignant biliary tract disease. As predictors of outcome following PTC are not well established, we sought to investigate outcomes after PTC and identify patients most at risk of complications. <h3>Method</h3> We performed a retrospective analysis of patients undergoing PTC between January 2012 and January 2014. <h3>Results</h3> 78 patients underwent 128 procedures. 85% of procedures were undertaken for malignant disease, of those, 50% were for palliative management only. Overall 30 day mortality was 21.8%. Multivariate analysis showed pre procedure serum albumin and development of acute kidney injury (AKI) post procedure to be significant independent predictors of mortality (p &lt; 0.05). AKI following PTC dramatically reduced median survival (11 days vs 114 days with no AKI, log rank p &lt; 0.05) and was associated with advancing age and higher pre procedure serum creatinine (p &lt; 0.05). Sepsis following PTC occurred in 61% but did not affect overall survival. <h3>Conclusion</h3> AKI following PTC is associated with increased mortality and patients at risk can be predicted by age and pre PTC creatinine. Identification of patients at risk, optimisation of renal function pre procedure and careful peri procedural management of fluid balance may help improve outcomes following PTC. <h3>Disclosure of interest</h3> None Declared.
Inflammation and the continuum model: time to acknowledge the molecular era of tendinopathy
Authors: Neal L Millar, Benjamin J Dean, Stephanie G Dakin
Journal: British Journal of Sports Medicine (2016)

The original continuum theory mentioned little concerning inflammatory mechanisms in tendon disease, likely due to the lack of scientific studies at that time. Since then, we and others have clearly defined a role for inflammatory cells1 and the subsequent inflammatory/matrix crosstalk involving cytokine regulation2 in human tendinopathy. It is …
Mir-126 Governs Human Leukemia Stem Cell Quiescence and Chemotherapy Resistance
Authors: Eric R. Lechman, Bernhard Gentner, Peter van Galen, Stanley Wai-Kwong Ng, Kolja Eppert, Rene Marke, Liran Slush, James A. Kennedy, Amanda Mitchell, Weihsu Claire Chen, Veronique Voisin, Gary Bader, Mark D. Minden, Jun Lu, Jean C.Y. Wang, Luigi Naldini, John E. Dick
Journal: Blood (2013)
Case 34-1978
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Robert S. Brown, Robert T. McCluskey
Journal: New England Journal of Medicine (1978)

Presentation of CaseA 27-year-old woman was admitted to the hospital because of renal failure.She was well and vigorous until two weeks previously, when peripheral edema developed, followed by progressive exertional dyspnea and severe, nonradiating back pain. She began to experience diffuse headaches and observed that her urine was dark orange. A physician found hypertension and proteinuria, advised omission of an oral contraceptive medication and prescribed hydrochlorothiazide and ampicillin. Eight days before admission the urea nitrogen was 54 mg; five days later it rose to 88 mg per 100 ml, and oliguria developed. She was referred to this hospital. . . .
PTH-207 Audit on appropriateness of trace element testing in patients on parenteral nutrition
Authors: N Vithanage, S Hoey, S Sital, H Callaby, R Prior, P Dubois, RP Vincent
Journal: Gut (2015)

<h3>Introduction</h3> Patients with intestinal failure/those not able to meet nutritional requirements via oral/enteral routes are on long term PN and prone to trace elements (TE) deficiencies. TE are added to the PN, based on recommended daily allowances but requires monitoring to optimise supplementations and we aimed to assess the clinical validity and appropriateness of TE testing in adult patients on PN. <h3>Method</h3> The retrospective audit reviewed all patients started on PN between March and July 2014. The audit standards were NICE nutrition guidelines on laboratory monitoring. It recommends TE testing at baseline and every 2–4 weeks. Acute phase responses can alter TE concentrations in the blood thus, confusing the interpretation of results. Therefore, it should always accompanied by CRP). Patients requiring PN &gt;2 weeks were included but those in critical care wards were excluded. Information was obtained from our PN database, pharmacy records and electronic patient records. The data was analysed for the% of appropriate requests,% in which phlebotomy was done and% availability of results. <h3>Results</h3> In total 21 patients (27%) received PN &gt;2 weeks. None of the patients had a baseline test. TE and CRP were ordered only in four patients (19%). Total number of requests for these patients was nine but phlebotomy was done only on three occasions (33%). All samples received by the lab were processed (100%). <h3>Conclusion</h3> Adherence to the NICE guidelines was very poor. The phlebotomy failure was multifactorial and is under review. A routine baseline TE test adds very little to clinical management as it is difficult to foresee which patients require PN &gt;2 weeks. Furthermore, from our previous experience TE should only be tested when CRP is &lt;20 mg/L which will exclude almost all critically ill/immediate post-op patients. <h3>Disclosure of interest</h3> None Declared.
Foreword
Authors: Mario U Mondelli, Roberto de Franchis, Massimo Colombo
Journal: Journal of Hepatology (2008)

The Journal of Hepatology supplement has become a fortunate tradition providing a high quality updated overview on liver diseases, therapy and management. This last edition represents a major effort of the Milan Editorial Office in an attempt to provide high quality, evidence-based updated information on what we think are the most challenging topics of modern hepatology. Our team of Associate Editors, as leading specialists in their own fields, gives us an excellent overview on the most important advances in hot areas of liver pathology worldwide. It is particularly rewarding that significant progress has been made in many fields and that basic research has largely become translational in nature, inasmuch as new concepts in liver disease management are now based on newly discovered basic pathogenetic mechanisms. The supplement focuses mostly on classical topics including cirrhosis and its complications, novel approaches to management of hepatocellular carcinoma, future treatment options of chronic hepatitis B, as well as fashionable topics of growing interest such as non-alcoholic fatty liver disease and classical ones such as iron, cholestasis and gallstones. The list has been deliberately limited to accommodate areas of major clinical relevance or those that needed appropriate updating. Over the past year, we have seen a significant rise of the Journal of Hepatology impact factor and we feel that this is the result of a joint effort between the old and the new Editorial Offices in the quest for scientific quality. The review articles of the supplement contain invaluable information which provide an excellent reference point for the widest readership. The Journal has now become an excellent means of conveying experimental data useful in clinical practice and it is precisely with this aim that the editors decided to produce a distillate of these in "Management of Liver Diseases 2008". We hope you like it. Last but not least, we wish to acknowledge the financial support of EASL without which this supplement could never have been published.
PWE-064 The clinical outcomes of a personalised approach to the management of patients taking thiopurine medication, using metabolite assessments
Authors: R Leyland, T Price, K Lithgo, D Housley, MW Johnson
Journal: Gut (2015)

<h3>Introduction</h3> A significant number of patients with inflammatory bowel disease (IBD) are treated with thiopurine drugs. Typically patients are commenced on starting doses of Azathioprine (AZA) or 6-Mercaptopurine (6-MP) and these are titrated up to 2.5 mg/kg and 1.25 mg/kg respectively, provided this is tolerated. Measurement of thiopurine metabolites (TPM), 6-Thioguanine nucleotide (6-TGN) and 6-Methylmercaptopurine nucleotide (6-MMPN), has proved useful in improving therapeutic efficacy, minimising unwanted side effects and identifying non-compliance. The aim of this study was to use TPM analysis to help guide the management of patients within our immunomodulator service, at the Luton and Dunstable University Hospital, taking thiopurine drugs. <h3>Method</h3> The gastroenterology department identified 406 patients with IBD who were taking thiopurine drugs. Letters were sent out on mass to these patients in December 2014 requesting a blood test for TPM before the end of January 2015. The patient’s samples were sent to Birmingham City Hospital for measurement of 6-TGN and 6-MMPN. A thiopurine management algorithm was designed to help clinicians understand these TPMs and direct them on how best to act on these results. <h3>Results</h3> Of the 406 patients who were sent TPM test requests, 200 attended prior to the end of January. These included 156 patients taking AZA and 44 taking 6-MP. The results for 6-TGN and 6-MMPN determined a change in management for 124 patients (62%), with only 76 patients (38%) classified as having an ‘accurate dose’ of AZA or 6-MP. Non-compliance with thiopurine therapy was evident for 15 patients (7.5%), and a further 5 patients phoned the IBD nurses directly admitting non-compliance. The dose of AZA or 6-MP was increased for 28 patients (14%) and decreased for 71 patients (35.5%). Thiopurine therapy was stopped in 10 patients (5%) due to significantly high levels of 6-TGN or 6-MMPN. A number of patients were classified as being ‘too sensitive’ to the thiopurine drugs with high concentrations of 6-MMPN. Based on the results of 6-TGN and 6-MMPN the drug used by 1 patient was changed from AZA to 6-MP. <h3>Conclusion</h3> The assessment of thiopurine metabolites directly led to the dose adjustment of AZA and 6-MP in 62% of patients tested. The measurement of 6-TGN and 6-MMPN enables appropriate personalised thiopurine dosing, following a simple thiopurine management algorithm, to optimise their therapy. Non-compliance is easy to identify and patients who preferentially metabolise thiopurine drugs to the hepatotoxic metabolite 6-MMPN had their therapy stopped, enabling initiation of alternative treatment modalities. Further work would be necessary to assess whether this reduces complications in the long term. <h3>Disclosure of interest</h3> None Declared.
Three Lessons
Authors: R M Magrisso
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 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
Propranolol Withdrawal
Authors: ROBERT ALLEN
Journal: Annals of Internal Medicine (1975)

Comments and Corrections1 March 1975Propranolol WithdrawalROBERT ALLEN, M.D., BRUCE GENOVESE, M.D.ROBERT ALLEN, M.D.Search for more papers by this author, BRUCE GENOVESE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-82-3-431_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: There have been several recent reports of severe exacerbations of symptoms in patients with coronary artery disease after the abrupt cessation of propranolol treatment (1,2). The authors have suggested tapering of the dose, rather than withdrawal, as a means of preventing this occurrence. We wish to report a case in which dose reduction alone appeared to precipitate symptoms.A 50-year-old white man with angina pectoris was admitted to the hospital for elective herniorrhaphy. The patient had been maintained on propranolol 40 mg four times daily and Isordil⌖ 20 mg every 4 hours, with relatively stable symptoms (angina...References1. MIZGALACOUNSELL HJ: Acute coronary syndromes following abrupt cessation of oral propranolol therapy. Circulation 50 (suppl 3):33, 1974 MedlineGoogle Scholar2. ALDERMANCOLDARTWEHACH EDG: Coronary artery syndromes after sudden propranolol withdrawal. Ann Intern Med 81:625-627, 1974 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Internal Medicine USAF Regional Hospital Maxwell Air Force Base, Alabama 36112 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAdverse reactions to drug withdrawalWithdrawal syndromes following cessation of treatment with antihypertensive drugsContemporary medical management of stable angina pectorisAbrupt propranolol withdrawal in angina pectoris: Effects on platelet aggregation and exercise toleranceBETA-BLOCKADE WITHDRAWALPropranolol-Withdrawal Rebound Phenomenon 1 March 1975Volume 82, Issue 3Page: 431-431KeywordsAnginaStable coronary artery disease ePublished: 1 December 2008 Issue Published: 1 March 1975 PDF downloadLoading ...
Fatal agranulocytosis in a chronic schizophrenic patient treated with carbamazepine
Authors: D J Luchins
Journal: American Journal of Psychiatry (1984)

A chronic schizophrenic patient developed a fatal agranulocytosis 1 month after beginning to take carbamazepine for aggression. Routine hematological monitoring was not carried out. This case highlights the need for psychiatrists' increased awareness of the possible hematological complications of carbamazepine.
Massachusetts Medical Society
Authors: John Figgis Jewett
Journal: New England Journal of Medicine (1982)

REPORT FROM THE COMMITTEE ON MATERNAL WELFAREFatal Respiratory DistressAn apparently healthy 29-year-old gravida II, para I whose first baby had died after premature birth at 25 weeks of gestation underwent cervical cerclage early in the second trimester of her second pregnancy. However, the membranes ruptured spontaneously at 29 weeks, and she was admitted at once to the local hospital.After uneventful observation for three days, the patient was sent home without treatment. Within 12 hours labor began, and the patient was readmitted —bleeding, febrile, and in active labor. The diagnosis of possible placenta previa was entertained, but the . . .