tbuckley/cabot-search huggingface dataset:
Histone H3 Lysine 79 Methyltransferase Dot1 Is Required for Immortalization by MLL Oncogenes
Authors: Ming-Jin Chang, Hongyu Wu, Nicholas J. Achille, Mary Rose Reisenauer, Chau-Wen Chou, Nancy J. Zeleznik-Le, Charles S. Hemenway, Wenzheng Zhang
Journal: Cancer Research (2010)

Abstract Chimeric oncoproteins resulting from fusion of MLL to a wide variety of partnering proteins cause biologically distinctive and clinically aggressive acute leukemias. However, the mechanism of MLL-mediated leukemic transformation is not fully understood. Dot1, the only known histone H3 lysine 79 (H3K79) methyltransferase, has been shown to interact with multiple MLL fusion partners including AF9, ENL, AF10, and AF17. In this study, we utilize a conditional Dot1l deletion model to investigate the role of Dot1 in hematopoietic progenitor cell immortalization by MLL fusion proteins. Western blot and mass spectrometry show that Dot1-deficient cells are depleted of the global H3K79 methylation mark. We find that loss of Dot1 activity attenuates cell viability and colony formation potential of cells immortalized by MLL oncoproteins but not by the leukemic oncoprotein E2a-Pbx1. Although this effect is most pronounced for MLL-AF9, we find that Dot1 contributes to the viability of cells immortalized by other MLL oncoproteins that are not known to directly recruit Dot1. Cells immortalized by MLL fusions also show increased apoptosis, suggesting the involvement of Dot1 in survival pathways. In summary, our data point to a pivotal requirement for Dot1 in MLL fusion protein–mediated leukemogenesis and implicate Dot1 as a potential therapeutic target. Cancer Res; 70(24); 10234–42. ©2010 AACR.
Narrow band imaging for colonoscopic surveillance in hereditary non-polyposis colorectal cancer
Authors: J E East, N Suzuki, M Stavrinidis, T Guenther, H J W Thomas, B P Saunders
Journal: Gut (2007)

Background: Colonoscopic surveillance for hereditary non-polyposis colorectal cancer (HNPCC) reduces death rates, but early interval cancers still occur, probably due to missed small, aggressive adenomas. Narrow band imaging (NBI), a novel endoscopic technology, highlights superficial mucosal capillaries and improves contrast for adenomas. This study examined whether a second pass with NBI in the proximal colon helped detect additional adenomas in patients with HNPCC. Methods: 62 patients from HNPCC families (Amsterdam II or genetic criteria) attending for colonoscopic surveillance were examined twice from caecum to sigmoid–descending junction, first with high definition white light and then a second pass with NBI in a back-to-back fashion. All polyps detected were removed for histopathological analysis. Results: At least one adenoma in the proximal colon was detected during the initial white light pass in 17/62 (27%). NBI detected additional adenomas in 17/62 (27%). 26/62 (42%) patients had at least one adenoma detected after both white light and NBI; absolute difference 15% (95% CI 4–25%), p = 0.004 versus white light alone. The total number of adenomas increased from 25 before NBI to 46 after NBI examination, p<0.001. The proportion of flat adenomas detected in the NBI pass, 9/21 (45%), was higher than in the white light pass, 3/25 (12%), p = 0.03. Including white light examination of the sigmoid and rectum, overall 28/62 (45%) patients had at least one adenoma detected. Conclusions: Use of NBI in the proximal colon for patients undergoing HNPCC surveillance appears to improve adenoma detection, particularly those with a flat morphology. NBI could help reduce interval cancer rates. ClinicalTrials.gov Identifier:NCT00313755.
Stability of surface NMDA receptors controls synaptic and behavioral adaptations to amphetamine
Authors: Li-Min Mao, Wei Wang, Xiang-Ping Chu, Guo-Chi Zhang, Xian-Yu Liu, Yuan-Jian Yang, Michelle Haines, Christopher J Papasian, Eugene E Fibuch, Shilpa Buch, Jian-Guo Chen, John Q Wang
Journal: Nature Neuroscience (2009)
Cysteinyl leukotriene involvement in chronic lung disease in premature infants
Authors: AJ Cook, B Yuksel, AP Sampson, A Greenough, JF Price
Journal: European Respiratory Journal (1996)

The pathophysiology of chronic lung disease (CLD) in premature infants who require mechanical ventilation and prolonged oxygen supplementation has been well-described but the underlying mechanisms are not understood. Our aim was to test the hypothesis that excess cysteinyl leukotriene (LT) production was a contributing factor in CLD. We compared LT production and lung function, at 7 months of age, in nine premature infants with CLD and in eight control infants without CLD. None of the control infants developed any neonatal respiratory problems, but two subsequently required bronchodilator therapy. Respiratory function was assessed by the measurement of thoracic gas volume (TGV), airways resistance (Raw) and functional residual capacity (FRC). Total cysteinyl LT production was quantified by measurement of leukotriene E4 (LTE4) in a spot urine sample. Although all patients were asymptomatic at follow-up, there was evidence of significant lung function abnormalities in infants with CLD. The CLD infants had significantly elevated TGV, Raw and FRC values reflecting airway obstruction when compared to the controls. Urinary LTE4 levels were significantly higher in the CLD infants when compared to the controls (geometric mean: 741 and 337 pmol.mmol-1 creatinine, respectively). There was no direct correlation between urinary LTE4 levels in the CLD group and TGV, Raw or FRC values. Although this study is small and a direct correlation between lung function and urinary leukotriene E4 was not demonstrated, pathological lung function and an enhanced urinary leukotriene E4 production in infants with chronic lung disease would tend to suggest that the cysteinyl leukotrienes were involved in the sequelae of this disease.
Evidence of healing of secondary hyperparathyroidism in chronically hemodialyzed uremic patients treated with long-term intravenous calcitriol
Authors: Giuseppe Cannella, Ermanno Bonucci, Davide Rolla, Paola Ballanti, Enzo Moriero, Roberta De Grandi, Carla Augeri, Franco Claudiani, Giovanni Di Maio
Journal: Kidney International (1994)
Applications of Magnetic Microbubbles for Theranostics
Authors: Xiaowei Cai, Fang Yang, Ning Gu
Journal: Theranostics (2012)

Compared with other diagnostic methods, ultrasound is proven to be a safe, simple, non-invasive and cost-effective imaging technique, but the resolution is not comparable to that of magnetic resonance imaging (MRI). Contrast-enhanced ultrasound employing microbubbles can gain a better resolution and is now widely used to diagnose a number of diseases in the clinic. For the last decade, microbubbles have been widely used as ultrasound contrast agents, drug delivery systems and nucleic acid transfection tools. However, microbubbles are not fairly stable enough in some conditions and are not well administrated distributed in the circulation system. On the other hand, magnetic nanoparticles, as MRI contrast agents, can non-specifically penetrate into normal tissues because of their relatively small sizes. By taking advantage of these two kinds of agents, the magnetic microbubbles which couple magnetic iron oxides nanoparticles in the microbubble structure have been explored. The stability of microbubbles can be raised by encapsulating magnetic nanoparticles into the bubble shells and with the guidance of magnetic field, magnetic microbubbles can be delivered to regions of interest, and after appropriate ultrasound exposure, the nanoparticles can be released to the desired area while the magnetic microbubbles collapse. In this review, we summarize magnetic microbubbles used in diagnostic and therapeutic fields, and predict the potential applications of magnetic microbubbles in the future.
European regulatory agencies should employ full time statisticians
Authors: Sara Hughes
Journal: BMJ (2008)

We would like to draw attention to what we believe is a major deficiency in European regulatory agencies that are responsible for reviewing applications to market new medicines across the whole of the European Union. Only agencies in the UK, Germany, Sweden, and Austria employ several full time statisticians, and a few others employ a single statistician. Some agencies that have a major role in the European regulatory process, such as those of Italy and Spain, do not employ any full time statisticians—instead they rely on external consultants.

Statistics is central to the design of clinical trials and to the interpretation of their results. Key regulatory guidelines such as ICH (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use) E3, E9, and E10 carry this clear message, as do numerous disease specific, clinical guidelines from CHMP (Committee for Medicinal Products for Human Use). The clinical trial component of regulatory submissions can be made up of the accumulated data from several thousand patients enrolled in several clinical trials. Evaluation of the data requires consideration of the impact of complex statistical issues relating to design of the trial and analysis of the data, such as bias in trial design, use of multiple end …
Comparison between Automatic and Fixed Positive Airway Pressure Therapy in the Home
Authors: Clifford A. Massie, Nigel McArdle, Robert W. Hart, Wolfgang W. Schmidt-Nowara, Alan Lankford, David W. Hudgel, Nancy Gordon, Neil J. Douglas
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

We tested the hypothesis that continuous positive airway pressure (CPAP) use and outcomes can be improved by an autotitrating CPAP device in patients with obstructive sleep apnea–hypopnea syndrome (OSAHS) who require higher CPAP (10 cm H2O or more). In this multisite randomized single-blind cross-over study, 44 patients (mean age, 49 ± 10 years) were randomized to 6 weeks at laboratory-determined fixed pressure and 6 weeks on autotitrating CPAP. Average nightly use was greater in automatic mode (306 versus 271 minutes, p = 0.005); median and 95th centile pressures in automatic mode were lower (p < 0.002). Automatic CPAP resulted in better SF-36 Vitality scores (65 ± 20 versus 58 ± 23, p < 0.05) and mental health scores (80 ± 14 versus 75 ± 18, p < 0.05), but no significant difference in Epworth score (p = 0.065). During automatic therapy, patients reported more restful sleep, better quality sleep, less discomfort from pressure, and less trouble getting to sleep for both the first week of therapy and for the averaged scores for Weeks 2–6 (all p values < 0.006). Patients who require higher fixed CPAP use autotitrating CPAP more and report greater benefit from this therapy.
Effect of Temperature on the Heart Rate, Electrocardiogram and Certain Myocardial Oxidations of the Rat
Authors: JOHN P. HANNON
Journal: Circulation Research (1958)

Deep hypothermia in the rat was studied with respect to the sequential changes in body temperature, heart rate, and electrocardiogram. In vitro assays of myocardial metabolic activity were made at temperatures ranging from 5 to 35 C. These assays strongly suggested that the in vivo cardiac dysfunctions observed at low temperatures were attributable to shifts in temperature kinetics of enzyme systems at 20 to 21 C.
High-Level Expression of the Coxsackievirus and Adenovirus Receptor Messenger RNA in Osteosarcoma, Ewing’s Sarcoma, and Benign Neurogenic Tumors among Musculoskeletal Tumors
Authors: Wenguang Gu, Akira Ogose, Hiroyuki Kawashima, Masayuki Ito, Tomoyuki Ito, Atsushi Matsuba, Hiroshi Kitahara, Tetsuo Hotta, Kunihiko Tokunaga, Hiroshi Hatano, Tetsuro Morita, Sayuri Urakawa, Tatsuya Yoshizawa, Hiroyuki Kawashima, Ryozo Kuwano, Naoto Endo
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The sensitivity of human tumor tissues to infection with recombinant adenoviruses correlates with the expression of the coxsackievirus and adenovirus receptor (CAR). CAR has been shown to function as the primary receptor for adenoviruses and to play a critical role in adenovirus entry into host cells. It is important for clinical gene therapy to determine the expression level of CAR in tumor tissues. Experimental Design: We analyzed the expression of CAR mRNA in 154 musculoskeletal tumor tissues from 154 patients and 10 normal mesenchymal tissues from 3 patients using reverse transcription-PCR and real-time quantitative PCR. An adenovirus infection assay was performed in two cell lines that were established from CAR-positive osteosarcoma tissue and CAR-negative malignant fibrous histiocytoma tissue. Results: Ninety-nine of 154 tumors were detected as CAR positive by reverse transcription-PCR. We found that the expression levels of CAR mRNA varied markedly between different tumors as determined by real-time quantitative PCR. CAR mRNA was expressed at high levels in osteosarcoma, Ewing’s sarcoma, neurofibroma, and schwannoma; at intermediate levels in exostosis, giant cell tumor, liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, and hemangioma; and at low levels in alveolar soft part sarcoma and desmoid. Whereas the osteosarcoma cell line that expressed a high level of CAR mRNA, like its parent tumor, had a high efficiency of adenovirus infection, the malignant fibrous histiocytoma cell line with almost undetectable expression of CAR mRNA, like its parent tumor, had a low efficiency of infection. Conclusions: Our data showed the great variations in CAR mRNA expression among human musculoskeletal tumors and mesenchymal tissues and implicated the potential usefulness of adenoviral vectors in gene therapy for osteosarcoma, Ewing’s sarcoma, neurofibroma, and schwannoma. Efficient transduction with adenovirus for gene therapy could be realized in appropriate, sensitive tumor types.
A Donne deal
Authors: Theodore Dalrymple
Journal: BMJ (2007)

John Donne, dean of St Paul's, is among the greatest poets in the English language. He was also a great meditator on disease: not surprisingly, perhaps, for in his day there was a lot of it about. In the 22nd of his Devotions on Emergent Occasions , which he wrote in response to a severe fever that nearly killed him, he says: “How ruinous a farme hath man taken, in taking himselfe! How ready is the house every day to fall downe, and how is all the ground overspread with weeds, all the body with diseases! where not onely every turfe, but every stone, beares weedes; not onely every muscle of the flesh, but every bone of the body, hath some infirmitie; every little flint upon the …
Gemcitabine and oxaliplatin combination chemotherapy in advanced biliary tract cancers
Authors: F. Verderame, A. Russo, R. Di Leo, G. Badalamenti, D. Santangelo, G. Cicero, M.R. Valerio, G. Gulotta, G. Tomasello, N. Gebbia, F. Fulfaro
Journal: Annals of Oncology (2006)
Proinflammatory cytokines upregulate expression of calprotectin (L1 protein, MRP-8/MRP-14) in cultured human keratinocytes
Authors: G. Mork, H. Schjerven, L. Mangschau, E. Soyland, P. Brandtzaeg
Journal: British Journal of Dermatology (2003)

Journal Article Proinflammatory cytokines upregulate expression of calprotectin (L1 protein, MRP‐8/MRP‐14) in cultured human keratinocytes Get access G. Mørk, G. Mørk Department of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar H. Schjerven, H. Schjerven Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, Rikshospitalet, N‐0027 Oslo, Norway Search for other works by this author on: Oxford Academic Google Scholar L. Mangschau, L. Mangschau Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, Rikshospitalet, N‐0027 Oslo, Norway Search for other works by this author on: Oxford Academic Google Scholar E. Søyland, E. Søyland Department of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar P. Brandtzaeg P. Brandtzaeg Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, Rikshospitalet, N‐0027 Oslo, Norway P.Brandtzaeg. E‐mail: per.brandtzaeg@labmed.uio.no Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue 3, 1 September 2003, Pages 484–491, https://doi.org/10.1046/j.1365-2133.2003.05536.x Published: 01 September 2003 Article history Accepted: 16 April 2003 Published: 01 September 2003
Was it a case of Takayasu arteritis?
Authors: M D Smith
Journal: Annals of the Rheumatic Diseases (2002)

Recently, the case of a 9 year old boy presenting with cardiac failure was presented in the Annals of the Rheumatic Diseases .1 It was reported as a case of Takayasu's arteritis in a child with a CD4+ lymphopenia and dysgammaglobulinaemia. I have a number of problems with this case:
HLA type of patients with coeliac disease and malignancy in the west of Ireland.
Authors: B R O'Driscoll, F M Stevens, T A O'Gorman, P Finnegan, J J McWeeney, M P Little, C E Connolly, C F McCarthy
Journal: Gut (1982)

HLA, A, B, and DR typing was done on seven of 10 patients with lymphoma, and six patients with carcinoma, all of whom had a flat small intestinal mucosa. Sixty-nine per cent (nine of 13) had HLA B8 and 71% (five of seven) had DR3. The corresponding levels for the local coeliac population are 76% and 84% respectively and the local non-coeliac population 43% and 44%. Two of the patients with lymphoma had a child with coeliac disease. The histological type of the lymphoma was malignant histiocytosis of the intestine in seven, histiocytic lymphoma in two, and was not classifiable in one. The similarity of the HLA type suggests that the flat mucosa in both groups is due to coeliac disease.
Privacy Protection During Internet Search for Health-Related Information—Reply
Authors: Marco D. Huesch
Journal: JAMA Internal Medicine (2014)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Randomised trial of MNrgp120 HIV-1 vaccine in symptomless HIV-1 infection
Authors: Joseph J Eron Jr, Mark A Ashby, Michael F Giordano, Marlene Chernow, William M Reiter, Steven G Deeks, James P Lavelle, Marcus A Conant, Bienvenido G Yangco, Perry G Pate, Ramón A Torres, Ronald T Mitsuyasu, Thomas Twaddell
Journal: The Lancet (1996)
Plasma Proneurotensin and Incidence of Diabetes, Cardiovascular Disease, Breast Cancer, and Mortality
Authors: Olle Melander, Alan S. Maisel, Peter Almgren, Jonas Manjer, Mattias Belting, Bo Hedblad, Gunnar Engström, Ute Kilger, Peter Nilsson, Andreas Bergmann, Marju Orho-Melander
Journal: JAMA (2012)

2][3][4] However, the causes of obesityassociated morbidity and mortality are poorly understood.6][7] Neurotensin binds to 3 different receptors: neurotensin receptor 1 and 2 (Ntsr1 and Ntsr2), which are G-protein coupled receptors, and neurotensin receptor 3 (Ntsr3), which is non-G-protein coupled and also known as sortilin-1 (SORT1). 8,9The peripheral secretion of neurotensin is stimulated by food intake, especially by fat, and is known to regulate gastrointestinal motility and
Diaphragm strength in chronic obstructive pulmonary disease.
Authors: M I Polkey, D Kyroussis, C H Hamnegard, G H Mills, M Green, J Moxham
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The diaphragm is normally the main inspiratory muscle and diaphragm strength in chronic obstructive pulmonary disease (COPD) is therefore of interest. We assessed diaphragm strength in 20 patients with severe stable COPD (mean FEV1 0.61, mean thoracic gas volume [Vtg] 5.31) and seven normal control subjects, measuring both maximal sniff transdiaphragmatic pressure (sniff Pdi(max)) and twitch transdiaphragmatic pressure (Tw Pdi) elicited by cervical magnetic stimulation (CMS) of the phrenic nerve roots at FRC. Acute-on-chronic hyperinflation was examined in four patients. Mean Tw Pdi in patients and control subjects was 18.5 cm H2O and 25.4 cm H2O, respectively (p < 0.01), and mean sniff Pdi was 81.9 cm H2O and 118 cm H2O, respectively (p < 0.001). Reduction in mean intrathoracic pressures was more marked; twitch esophageal pressure (Tw Pes) was -7.3 cm H2O and -16.3 cm H2O, respectively (p < 0.001) and sniff Pes was -67 cm H2O and -97.8 cm H2O (p < 0.001). During acute-on-chronic hyperinflation there was a linear negative correlation of Tw Pdi with increasing lung volume of 3.5 cm H2O/L. The ability of the diaphragm to generate transdiaphragmatic, and particularly a negative intrathoracic, pressure is reduced in COPD and these changes are exaggerated with acute-on-chronic hyperinflation.
Market and patient access to new oncology products in Europe: a current, multidisciplinary perspective
Authors: C. McCabe, L. Bergmann, N. Bosanquet, M. Ellis, H. Enzmann, M. von Euler, B. Jönsson, K.-J. Kallen, D. Newling, V. Nüssler, B. Paschen, R. de Wilde, N. Wilking, C. Teale, H. Zwierzina
Journal: Annals of Oncology (2008)
Imaging sites of airway obstruction and measuring functional responses to bronchodilator treatment in asthma.
Authors: S K Chopra, G V Taplin, D P Tashkin, E Trevor, D Elam
Journal: Thorax (1979)

The sites of airway obstruction and dilatation after terbutaline administration were studied by inhalation imaging and pulmonary function tests in 12 stable asthmatic patients. Inhaled terbutaline as a therapeutic aerosol decreased airway resistance (Raw) and improved radioaerosol (Ae) images in nine, delta V max50 in three, and xenon (Xe) images in five of 12 subjects, suggesting that its predominant site of action was on major airways. Subcutaneously injected terbutaline improved Raw, delta V max50, and Ae images in 11 and Xe images in eight subjects indicating that it released bronchospasm in the major and minor airways. These findings in asthma suggest that aerosol and Xe imaging procedures are sensitive indicators of large and small airway obstruction respectively.