tbuckley/cabot-search huggingface dataset:
Long Noncoding RNA HULC Modulates Abnormal Lipid Metabolism in Hepatoma Cells through an miR-9–Mediated RXRA Signaling Pathway
Authors: Ming Cui, Zelin Xiao, Yue Wang, Minying Zheng, Tianqiang Song, Xiaoli Cai, Baodi Sun, Lihong Ye, Xiaodong Zhang
Journal: Cancer Research (2015)

Abstract HULC is a long noncoding RNA overexpressed in hepatocellular carcinoma (HCC), but its functional contributions in this setting have not been determined. In this study, we explored the hypothesis that HULC contributes to malignant development by supporting abnormal lipid metabolism in hepatoma cells. HULC modulated the deregulation of lipid metabolism in HCC by activating the acyl-CoA synthetase subunit ACSL1. Immunohistochemical analysis of tissue microarrays revealed that approximately 77% (180/233) of HCC tissues were positive for ACSL1. Moreover, HULC mRNA levels correlated positively with ACSL1 levels in 60 HCC cases according to real-time PCR analysis. Mechanistic investigations showed that HULC upregulated the transcriptional factor PPARA, which activated the ACSL1 promoter in hepatoma cells. HULC also suppressed miR-9 targeting of PPARA mRNA by eliciting methylation of CpG islands in the miR-9 promoter. We documented the ability of HULC to promote lipogenesis, thereby stimulating accumulation of intracellular triglycerides and cholesterol in vitro and in vivo. Strikingly, ACSL1 overexpression that generates cholesterol was sufficient to enhance the proliferation of hepatoma cells. Further, cholesterol addition was sufficient to upregulate HULC expression through a positive feedback loop involving the retinoid receptor RXRA, which activated the HULC promoter. Overall, we concluded that HULC functions as an oncogene in hepatoma cells, acting mechanistically by deregulating lipid metabolism through a signaling pathway involving miR-9, PPARA, and ACSL1 that is reinforced by a feed-forward pathway involving cholesterol and RXRA to drive HULC signaling. Cancer Res; 75(5); 846–57. ©2015 AACR.
Does IV heparin after streptokinase prevent left ventricular thrombus in acute anterior myocardial infarction?: a randomised, prospective, double blind, placebo controlled study
Authors: A.A. Gehani, F.R.C.P. Edin, F. Mahrous, A. Ammar, M. Dosouky, H.A. Hajar
Journal: Journal of the American College of Cardiology (1998)
Education and Training for Primary Care Internal Medicine
Authors: MICHAEL L. FRIEDLAND
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 June 1985Education and Training for Primary Care Internal MedicineMICHAEL L. FRIEDLAND, M.D.MICHAEL L. FRIEDLAND, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-6-862_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The recent article by Kosecoff and associates (1) and editorial by Huth (2) suggest that the efforts of academic medical centers to promote primary care internal medicine in the last 10 to 15 years have not fulfilled their early promise. This lack of success in both the quality of programs and numbers of students selecting primary care—coupled with my recollections of Petersdorf's address at the 1976 commencement of Brown University, the GPEP Report (3), and my own observations as an internist, program director, and teacher for 15 years—leads me to propose the following suggestions.All entering first-year...References1. KOSECOFFFINKBROOK JAR. General medical care and the education of internists in university hospitals: an evaluation of the teaching hospital general medicine group practice program. Ann Intern Med. 1985;102:250-7. LinkGoogle Scholar2. HUTH E. The academic future of general internal medicine [Editorial]. Ann Intern Med. 1985;102:261-3. LinkGoogle Scholar3. . Physicians for the Twenty-First Century: The GPEP Report: Report of the Panel on the General Professional Education of the Physician and College Preparation of Medicine. Washington, D.C.: Association of American Medical Colleges; 1984. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: MICHAEL L. FRIEDLAND, M.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPreventive Medicine and Residency TrainingRALPH G. GREENLEE, M.D. 1 June 1985Volume 102, Issue 6Page: 862-862KeywordsAcademic medicineMedical education ePublished: 1 December 2008 Issue Published: 1 June 1985 PDF downloadLoading ...
PMO-112 Is primary biliary cirrhosis a steroid sensitive autoimmune disease?
Authors: A Dhanda, R Lee, P L Collins
Journal: Gut (2012)

<h3>Introduction</h3> Primary biliary cirrhosis (PBC) is a classic T cell mediated autoimmune disease: an autoantigen has been described and high levels of antigen specific liver infiltrating auto-reactive CD4<sup>+</sup> T cells found. However, unlike in other autoimmune conditions steroid therapy is not considered effective in PBC although there is existing evidence that it can improve histological and biochemical parameters.<sup>1</sup> We sought further evidence that PBC is a steroid sensitive disease by using two in vitro measures of steroid sensitivity. <h3>Methods</h3> We have applied an in vitro dexamethasone (Dex) inhibition of lymphocyte proliferation assay (DILPA), which correlates well with clinical steroid sensitivity and outcome in ulcerative colitis<sup>2</sup> and alcoholic hepatitis,<sup>3</sup> to 20 patients with PBC diagnosed by liver biochemistry, antibodies and liver histology (when performed). The DILPA assesses peripheral blood mononuclear cell (PBMC) sensitivity to treatment with steroids in vitro. We also examined the role of CD14<sup>+</sup> monocytes, which produce pro-inflammatory cytokines to recruit T cells to the tissue of inflammation. PBMCs were isolated from peripheral blood by density gradient centrifugation over Ficoll. CD14<sup>+</sup> cells were obtained by positive microbead selection and cultured with 300 ng/ml lipopolysaccharide in the presence or absence of Dex 1×10<sup>−6</sup>M for 24 h. Supernatants were then collected and interleukin (IL)-1β, IL-6 and TNFα were measured by cytokine bead array (BD biosciences) according to manufacturer9s instructions. Suppression of cytokine production by Dex was calculated. <h3>Results</h3> In 20 patients with PBC, just one individual demonstrated in vitro steroid resistance by DILPA, and peripheral lymphocytes were sensitive to steroids in all other study subjects. Suppression of lymphocyte proliferation by Dex was significantly greater in patients with PBC compared to 37 healthy volunteer controls (86% vs 76%, p=0.04). Furthermore, Dex induced a 40%–100% suppression of IL-1β, IL-6 and TNFα (mean 75%, 74% and 79%, respectively) in the supernatants of CD14<sup>+</sup> monocyte cultures. This suggests that both peripheral blood lymphocytes and monocytes in patients with PBC are steroid sensitive. <h3>Conclusion</h3> Using a validated measure of lymphocyte steroid sensitivity and a further assessment of monocyte steroid sensitivity we have demonstrated that PBC is a steroid sensitive disease. Together with existing clinical studies of glucocorticoids in PBC<sup>1</sup> our in vitro evidence suggests that steroid treatment should not be dismissed outright as it may provide a useful option in selected patients with PBC. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Mitchison HC</b>, <i>et al</i>. <i>Hepatology</i> 1989;<b>10</b>:420–9. 2. <b>Hearing SD</b>, <i>et al</i>. <i>Gut</i> 1999;<b>45</b>;382–8. 3. <b>di Mambro AJ</b>, <i>et al</i>. <i>Hepatology</i> 2011;<b>53</b>:1316–22.
A step change in operational performance is needed
Authors: J. Moulton, A. Woodcock, H. P. Critchley
Journal: BMJ (2010)

The JP Moulton Charitable Foundation began funding non-commercial clinical trials in April 2004. Applications had to demonstrate good scientific rationale, expertise in the area of research, clear budget breakdowns, and achievable targets. If funding was approved, the foundation requested a detailed breakdown of costs, milestones for payment against recruitment, detailed quarterly progress reports, and …
Abstract 2599: Inhibitory effects of new 1H-pyrrolo[3,2-c]pyridine derivative, KIST101029, on AP-1 activity and neoplastic cell transformation induced by insulin-like growth factor 1.
Authors: Hyo Jeong Yun, Hong Seok Choi
Journal: Cancer Research (2013)

Abstract Diarylureas and diarylamides derivatives are reported to have antitumor activity. Encouraged by the interesting antiproliferative activity of diarylurea and diarylamide derivatives, we synthesized a new series of diarylureas and diarylamides containing pyrrolo[3,2-c]pyridine scaffold. In this study, we demonstrate that a new 1H-pyrrolo[3,2-c]pyridine derivative, KIST101029, inhibits neoplastic cell transformation induced by insulin-like growth factor 1 (IGF-1) in mouse epidermal JB6 Cl41 cells. The KIST101029 compound inhibited mitogen-activated protein kinase/extracellular signal-regulated kinase kinases (MEK), c-jun N-terminal kinases (JNK), and mechanistic target of rapamycin (mTOR) signaling pathways induced by IGF-1 in JB6 Cl41 cells, resulting in the inhibition of c-fos and c-jun transcriptional activity. In addition, the KIST101029 inhibited the associated activator protein-1 (AP-1) transactivation activity and cell transformation induced by IGF-1 in JB6 Cl41 cells. Consistent with these observations, in vivo chorioallantoic membrane assay also showed that the KIST101029 inhibited IGF-1-induced tumorigenicity of JB6 Cl41 cells. Taken together, these results indicate that a new 1H-pyrrolo[3,2-c]pyridine derivative, KIST101029, might exert chemopreventive effects through the inhibition of phosphorylation of MAPK and mTOR signaling pathway. Citation Format: Hyo Jeong Yun, Hong Seok Choi. Inhibitory effects of new 1H-pyrrolo[3,2-c]pyridine derivative, KIST101029, on AP-1 activity and neoplastic cell transformation induced by insulin-like growth factor 1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2599. doi:10.1158/1538-7445.AM2013-2599 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Charity donations in name of UK doctor killed in Syria rise beyond expectations
Authors: S. Arie
Journal: BMJ (2013)

A call for donations to pay tribute to a British doctor killed while volunteering in Syria has so far raised over £58 000 (€68 000; $88 000), which the charity he worked for will use to set up a field hospital in his name.

Isa Abdur Rahman, a 26 year old from London, was killed in Syria on 22 May when the secret hospital he was working in was bombed. The doctor, who qualified at Imperial College London, had been working in Syria with the British organisation Hand in Hand for Syria for the past year. …
Dual Therapeutic Utility of Proteasome Modulating Agents for Pharmaco-gene Therapy of the Cystic Fibrosis Airway
Authors: Liang N. Zhang, Phil Karp, Christopher J. Gerard, Eric Pastor, Douglas Laux, Keith Munson, Ziying Yan, Xiaoming Liu, Simon Godwin, Christie P. Thomas, Joseph Zabner, Huidong Shi, Charles W. Caldwell, Richard Peluso, Barrie Carter, John F. Engelhardt
Journal: Molecular Therapy (2004)

Pharmacologic- and gene-based therapies have historically been developed as two independent therapeutic platforms for cystic fibrosis (CF) lung disease. Inhibition of the dysregulated epithelial Na channel (ENaC) is one pharmacologic approach to enhance airway clearance in CF. We investigated pharmacologic approaches to enhance CFTR gene delivery with recombinant adeno-associated virus (rAAV) and identified compounds that significantly improved viral transduction while simultaneously inhibiting ENaC activity through an unrelated mechanism. Treatment of human CF airway epithelia with proteasome modulating agents (LLnL and doxorubicin) at the time of rAAV2 or rAAV2/5 infection dramatically enhanced CFTR gene delivery and correction of CFTR-mediated short-circuit currents. Surprisingly, these agents also facilitated long-term (15-day) functional inhibition of ENaC currents independent of CFTR vector administration. Inhibition of ENaC activity was predominantly attributed to a doxorubicin-dependent decrease in gamma-ENaC subunit mRNA expression and an increase in gamma-ENaC promoter methylation. This is the first report to describe the identification of compounds with dual therapeutic action that are able to enhance the efficacy of CFTR gene therapy to the airway while simultaneously ameliorating primary aspects of CF disease pathophysiology. The identification of such compounds mark a new area for drug development, not only for CF, but also for other gene therapy disease targets.
Improved Cardiac Iodine-123 Metaiodobenzylguanidine Accumulation After Drug Therapy in a Patient With Parkinson's Disease
Authors: NORIKO KANZAKI, KEIKO SATO, TOSHIYUKI HAYABARA
Journal: Clinical Nuclear Medicine (1997)

A 72-year-old woman with Parkinson's disease and autonomic dysfunction underwent I-123 MIBG cardiac imaging to study sympathetic neuronal integrity. This revealed a defect in the infero-posterior wall. Tc-99m sestamibi myocardial perfusion imaging revealed no abnormalities. On follow-up I-123 MIBG SPECT, the defect was less prominent and the parkinsonian symptoms were ameliorate by drug therapy. Cardiac I-123 MIBG imaging may be a promising new method for evaluating drug therapy in patients with Parkinson's disease.
Verrucous localized lymphedema of genital areas: Clinicopathologic report of 18 cases of this rare entity
Authors: Jose A. Plaza, Luis Requena, Dmitry V. Kazakov, Elisa Vega, Denisa Kacerovska, Gisela Reyes, Michal Michal, Saul Suster, Martin Sangueza
Journal: Journal of the American Academy of Dermatology (2014)
Rservoir of group B streptococci in women in labour.
Authors: F S Mhalu
Journal: BMJ (1977)

Methods and resultsTo have a basis for comparison, we measured urea, creatinine, and a-fetoprotein (a-FP) concentrations in maternal urine and amniotic fluid collected from 30 patients undergoing second trimester amniocentesis.Urine samples were midstream specimens collected before the patients underwent transabdominal amniocentesis.After centrifuging both samples at 1000 rpm, we estimated the urea creatinine, and a-FP concentrations.The different concentration of each substance in amniotic fluid and maternal urine is clearly illustrated in the table.Urea, creatinine, and a-fetoprotein concentrations in amnioticfluid and maternal urine (means and ranges) Test Amniotic fluid Maternal urine Urea (mmol/l) 1-83 (0-83-3-49) 47-1 (19 9-106 2)Creatinine (,umol/l) 71 (53-97) 3801 (1060-13 437) a-fetoprotein (mg/l) 18-6 (4-0-34-0) 0-005 (<0 005-0-026) Conversion: SI to traditional units-Urea: 1 mmol/l16 mg/100 ml.Creatinine: 1 tmol/l 0-0113 mg/100 ml.
Research and Training Programs in General Internal Medicine
Authors: WILLIAM M. TIERNEY
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 July 1982Research and Training Programs in General Internal MedicineWILLIAM M. TIERNEY, M.D.WILLIAM M. TIERNEY, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-1-136_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The plea by Drs. Griner and Huth (1) for increased involvement of general internal medicine faculty members in research activities is timely. There is an urgent need not only for general internists to do research (to further their academic careers and to lend academic credibility to the general internal medicine unit), but also for questions to be investigated that would best be done by general internists. These are questions on health care delivery, clinical decision making, and medical education, as well as those regarding disease entities that clearly cross subspecialty lines (for example, the evaluation of syncope)....References1. GRINERHUTH PE. Research in general internal medicine [Editorial]. Ann Intern Med. 1982;96:518-9. LinkGoogle Scholar2. FRIEDMANPOZENROSENCRANSEISENBERGGERTMAN RJAJP. General internal medicine units in academic medical centers: their emergence and functions. Ann Intern Med. 1982;93:233-8. LinkGoogle Scholar3. Research training and support programs of special interest to young physician investigators. Clin Res. 1982;30:130-8. Google Scholar1. FRIEDMANPOZENROSENCRANSEISENBERGGERTMAN RJAJP. General internai medicine units in academic medical centers: their emergence and functions. Ann Intern Med. 1982;96:233-8. LinkGoogle Scholar2. TARLOV A. Academic general internal medicine [Editorial]. Ann Intern Med. 1982;96:239-40. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1982Volume 97, Issue 1Page: 136-137KeywordsAcademic medicineDecision makingHealth careMedical educationSub-specialty careSyncope Issue Published: 1 July 1982 PDF downloadLoading ...
The transformation of maternal mortality.
Authors: I. Loudon
Journal: BMJ (1992)

ence now of such differentials in societies with very different social structures to those of Britain today.When Chapin documented mortality differentials in Providence in 1924 he hoped that such a demonstration would be preparation for "what should be of great value, namely a study of the habits of life and environment which make for the longevity of the well-to-do."28This still pertains.
Intensive insulin therapy and starch (HES 200/0.5) had some risk and no clear benefit in severe sepsis
Authors: Deborah Cook
Journal: Annals of Internal Medicine (2008)

ACP Journal Club17 June 2008Intensive insulin therapy and starch (HES 200/0.5) had some risk and no clear benefit in severe sepsisDeborah Cook, MD, Lauralyn McIntyre, MDDeborah Cook, MDMcMaster University, Hamilton, Ontario, Canada (D.C.)Search for more papers by this author, Lauralyn McIntyre, MDUniversity of Ottawa, Ottawa, Ontario, Canada (L.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-148-12-200806170-02004 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationBrunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358:125-39. https://pubmed.ncbi.nlm.nih.gov/18184958Clinical Impact RatingsEmergency Med: Hospitalists: Infectious Disease: Critical Care: References1 Zarychanski R, Turgeon AF, Fergusson DA, et al. Renal outcomes following hydroxylethyl starch resuscitation: a meta-analysis of randomized trials [abstract]. Intensive Care Med (submitted). Google Scholar2 van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359-67. [PMID: 11794168] Google Scholar3 A multi-centre, open-label randomized stratified controlled trial of the effects of blood glucose management on 90-day all-cause mortality in a heterogeneous population of intensive care unit patients. www.controlled-trials.com/ISRCTN04968275 (accessed on 25 April 2008). Google Scholar Author, Article, and Disclosure InformationAffiliations: McMaster University, Hamilton, Ontario, Canada (D.C.)University of Ottawa, Ottawa, Ontario, Canada (L.M.)This article was published at Annals.org on 3 June 2008. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 June 2008Volume 148, Issue 12Page: JC4-4KeywordsAcute renal failureHypoglycemiaInsulinIntensive care unitsResuscitationSepsisStarches ePublished: 17 June 2008 Issue Published: 17 June 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Bony Tumour of the Breast
Authors: W. H. G. M. Ling, I. S. Stewart
Journal: BMJ (1955)

MEDICAL MEMORANDA BDIORNAL evening had taken a dose of sodium sulphate for constipation, which he associated with the pains.On admission the patient was severely shocked and in great pain.The diagnosis was acute pancreatitis, perforation to be excluded.At operation there was a large quantity of beef-juice fluid in the abdomen; the pancreas was swollen and firm, with much oedema of the loose tissues over it.A drain was placed in the lesser sac and the abdomen closed.Convalescence was stormy, chiefly owing to the development of ileus and acute renal failure.On the seventh day the patient seemed dangerously ill with oliguria, drowsiness, hiccup, poor general condition, and a total non-protein nitrogen level of 150 mg. per 100 ml.blood.However, on the tenth day the urinary output increased and he improved.He was discharged on October 28, 1946.He was readmitted on September 17, 1948, just two years later.He had been having attacks of severe pain about once a month, with more frequent minor episodes.Diet and laxatives gave no relief.He could not take any fatty foods.Saline aperients produced pain, so for the past nine months he had been using an enema.On this second occasion the
Investigating Intergenerational Differences in Human PCB Exposure due to Variable Emissions and Reproductive Behaviors
Authors: Cristina L. Quinn, Frank Wania, Gertje Czub, Knut Breivik
Journal: Environmental Health Perspectives (2010)

Reproductive behaviors--such as age of childbearing, parity, and breast-feeding prevalence--have changed over the same historical time period as emissions of polychlorinated biphenyls (PCB) and may produce intergenerational differences in human PCB exposure.Our goal in this study was to estimate prenatal, postnatal, and lifetime PCB exposures for women at different ages according to year of birth, and to evaluate the impact of reproductive characteristics on intergenerational differences in exposure.We used the time-variant mechanistic model CoZMoMAN to calculate human bioaccumulation of PCBs, assuming both hypothetical constant and realistic time-variant emissions.Although exposure primarily depends on when an individual was born relative to the emission history of PCBs, reproductive behaviors can have a significant impact. Our model suggests that a mother's reproductive history has a greater influence on the prenatal and postnatal exposures of her children than it does on her own cumulative lifetime exposure. In particular, a child's birth order appears to have a strong influence on their prenatal exposure, whereas postnatal exposure is determined by the type of milk (formula or breast milk) fed to the infant.Prenatal PCB exposure appears to be delayed relative to the time of PCB emissions, particularly among those born after the PCB production phaseout. Consequently, the health repercussions of environmental PCBs can be expected to persist for several decades, despite bans on their production for > 40 years.