tbuckley/cabot-search huggingface dataset:
Effect of Human Growth Hormone on Hypoglycemic States
Authors: W. A. Mahon, M. L. Mitchell, J. Steinke, M. S. Raben
Journal: New England Journal of Medicine (1962)

THE administration of small doses of purified preparations of human growth hormone to patients with diabetes mellitus may produce profound changes in the metabolism of carbohydrate, resulting in elevations in blood sugar and the appearance of ketoacidosis.1 2 3 It is of interest that despite the "anti-insulin" effects of human growth hormone, especially in hypophysectomized diabetic patients,4 , 5 small doses of this hormone have had little or no effect upon carbohydrate metabolism in normal subjects6 7 8 or in panhypopituitary dwarfs,9 but few studies have been carried out with human growth hormone in conditions of altered carbohydrate metabolism caused by conditions other than diabetes mellitus. . . .
Abstract 2336: SFRP4 expression as a marker of invasion in gastric cancer
Authors: Rita A. Busuttil, Joshy George, Kylie Scott, Patrick Tan, Stephen Lade, David D. Bowtell, Alex Boussioutas
Journal: Cancer Research (2011)

Abstract Gastric cancer (GC) is the fourth most common cancer in the world with approximately 1 million patients being diagnosed annually and is the second highest cause of cancer related deaths worldwide resulting in 700,000 deaths per year. The advanced stage at diagnosis and limited curative treatments for this stage of disease explains the mortality rate for GC. Early and late GC can usually be differentiated by their T-stage, which is a measure of invasion of the tumour through the gastric wall. T1 tumours exhibit minimal invasion whilst T4 tumours have invaded into adjacent structures. Through our genomic research we have identified SFRP4 as a gene that is consistently over-expressed in gastric cancer when compared to normal gastric tissue, particularly advanced stage cancer. Its gene expression levels are directly proportional to the degree of invasion suggesting a potential role in this process. Analysis of the clinical data in conjunction with the genomics data shows that elevated levels of SFRP4 have also been correlated with poor prognosis in patients with GC independent of their T-stage. We have used shRNA knockdown of SFRP4 in a gastric cell line to validate these findings in vitro. The invasive phenotype is able to be restored in these cells with the addition of recombinant SFRP4 protein. Evidence from this study suggests that SFRP4 plays a role in invasion which is a fundamental property of all cancers. In vivo studies are currently underway to determine whether the functional effects of SFRP4 observed in vitro in gastric cancer lines can be recapitulated in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2336. doi:10.1158/1538-7445.AM2011-2336
Graduate Medical Education in the Freddie Gray Era
Authors: Sammy Zakaria, Erica N. Johnson, Jennifer L. Hayashi, Colleen Christmas
Journal: New England Journal of Medicine (2015)

In the wake of the death of Freddie Gray and the protests over unjust treatment of black Americans, the internal medicine residency program at Johns Hopkins launched a curriculum aiming to provide tools for improving population health and reducing health disparities.
Tc-99m Pyrophosphate Uptake in Small Areas of Myocardial Injury Produced by Radiofrequency Catheter Ablation of Arrhythmias
Authors: Hee-Seung Bom, Jeong-Gwan Cho, Ho-Cheon Song, Jung-Jun Min, Hwan-Jeong Jeong, Ji-Yeul Kim, Jung-Chaee Kang
Journal: Clinical Nuclear Medicine (1999)

Radiofrequency produces small circumscribed areas of myocardial damage and is now used most commonly for ablation of arrhythmias. The proper position of a catheter can be determined easily by fluoroscopy. However, the degree of tissue destruction cannot be assessed by electronic or radiographic techniques. Seventeen patients with arrhythmia were studied 2 days after radiofrequency catheter ablation of arrhythmias by Tc-99m pyrophosphate scintigraphy. In 14 of the 17 patients (82.4%), myocardial lesions produced by radiofrequency ablation were successfully demonstrated by SPECT imaging, whereas none showed positive uptake on planar images. Two cases are illustrated.
Hemitruncus Anomaly as a Cause of Unilateral Absent Lung Perfusion With Normal Ventilation on Radionuclide Lung Scan
Authors: ROBERT LISBONA, VILMA DERBEKYAN, JAVIER A. NOVALES-DIAZ
Journal: Clinical Nuclear Medicine (1996)

There are numerous causes for unilateral absence of lung perfusion on Tc-99m MAA imaging. Systemic perfusion of the involved lung with pulmonary artery agenesis should be added to the list.
FRI0344 Safety and efficacy of etanercept in juvenile idiopathic arthritis patients under two years of age:
Authors: G. Horneff
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In Juvenile Idiopathic Arthritis (JIA) patients Etanercept is an effective therapeutic agent with an excellent safety profile. Currently it is licensed for treatment in polyarticular JIA patients over the age of 2 years. <h3>Objectives</h3> To assess the efficacy and safety of Etanercept in JIA patients below the age of 2 years. <h3>Methods</h3> The data base of the German BIKER registry documenting the treatment of 1499 JIA patients with Etanercept since 2001 has been used to identify patients who started treatment before the age of 2 years. Efficacy of treatment will be analyzed by achieving the ACRped30/50/70 criteria and single contributing domains. Safety analysis was performed on the basis of adverse event reports. <h3>Results</h3> 7 patients (2 female) with a median age of 22.4 months (range 14-23 months) were identified. JIA category distribution varied from the total cohort: 4 had systemic JIA, 2 extended oligoarthritis and 1 seronegative polyarthitis. ANA were present in 2/6 pts, one pt had concomitant chronic uveitis. 3 received measles and 1 received varicella vaccination before start of Etanercept. All pts had received non-steroidal antirheumatic drugs, 6/7 methotrexate and 1 pt Cyclosporine A. The median initial weekly dosage of Etanercept was 0.8 mg/kg (0.66-1.05). 3 patients received once once weekly injections. Concomitant treatments were corticosteroids (n=2), methotrexate (n=7) and cyclosporine A (n=1). At 3 months the ACR response levels were: ACR ped30, 86%; ACRped50, 71%; ACRped70, 57%; at 6 months: ACR ped30, 83%; ACRped50, 83%; ACRped70, 83%; at 12 months ACR ped30, 80%; ACRped50, 60%; ACRped70, 60%; at the last observation with Etanercept: ACR ped30, 71%; ACRped50, 71%; ACRped70, 71%. Furthermore, Etanercept provided clinically meaningful improvement for, Physician global assessment of disease activity; number of active joints, Childhood health assessment questionnaire disability index, ESR and CRP (Table). Upon treatment, there were two adverse events in 2 patients; one pneumonia and one uveitis flare, one patient developed Hodgkin's disease 5 years later. One patient discontinued Etanercept for inefficacy, 4 for reaching remission of their disease and one due to an adverse event (uveitis). <h3>Conclusions</h3> In this small cohort of very young patients Etanercept proved safe and efficacious in the majority of children. The response as well as the tolerability was similar to that in older children. These preliminary results suggest that Etanercept therapy is a suitable and efficacious treatment option for patients with JIA under the age of two years. Further long term safety data are needed. The German BIKER registry is supported by Pfizer Pharma <h3>Disclosure of Interest</h3> G. Horneff Grant/Research support from: Pfizer, Abbott
PTU-147 Incidence and Predictive Features of Pharyngeal Pouches in a Dysphagic Population: Abstract PTU-147 Table
Authors: I A Murray, H R Dalton, J Palmer, A D Wilde, D R Grimes
Journal: Gut (2013)

<b>228</b> <h3><b>Objectives</b></h3> The folate receptor (FR) is a promising molecular target for cancer therapy as it is expressed by many epithelial cancers and not in most healthy cells. Vintafolide, a small-molecule drug conjugate of folate and a potent vinca alkaloid, is currently being evaluated in clinical trials. <sup>99m</sup>Tc-etarfolatide, a folate-based imaging agent, can noninvasively identify FR-positive lesions and may help to identify patients who could benefit from vintafolide. This phase 1 trial aimed to determine the safety/tolerability and biodistribution/excretion of <sup>99m</sup>Tc-etarfolatide in the presence/absence of folic acid (FA) preinjections in healthy volunteers. <h3><b>Methods</b></h3> Participants (n=20) received <sup>99m</sup>Tc-etarfolatide with no FA (0.1 mg IV, 20-25 mCi) on day 1 (image timepoint 1). Before the second dose (on day 5, 6, or 7; image timepoint 2) they received 0.5 mg (n=11) or 1.0 mg (n=9) IV FA. Participants underwent whole-body planar imaging (timepoint 1: at 1 hr; timepoint 2: at 5 min and 1, 4, 6-8, 20-24 hr) and SPECT scan (chest, abdomen, and pelvis; both timepoints: at 1-1.5 hr postinjection). Blood and urine samples for hematology, serum, and urinalysis analyses were obtained at multiple timepoints. Adverse events were registered for 4 days. <h3><b>Results</b></h3> The liver (17%) and red marrow (16%) had the highest peak <sup>99m</sup>Tc-etarfolatide uptake (timepoint 2). The largest dose equivalent was received by the urinary bladder wall and kidneys (0.026 and 0.025 mSv/MBq). The mean effective dose was 0.0076 mSv/MBq. <sup>99m</sup>Tc-etarfolatide’s α clearance half-life was 26.9 min. The kidneys were the major route of elimination (41% recovery/24 hr). FA preinjection decreased radiation exposure in most organs, but the higher FA dose did not greatly impact dosimetry values. In all cases, the blinded nuclear medicine radiologist scored the overall global background uptake in organs as lower on scans where patients received FA preinjection. <sup>99m</sup>Tc-etarfolatide was well tolerated. <h3><b>Conclusions</b></h3> In healthy volunteers,<sup>99m</sup>Tc-etarfolatide distributes mainly to the bladder, kidneys, and liver. A FA pre-injection reduces background uptake in organs and therefore potentially optimizes <sup>99m</sup>Tc-etarfolatide imaging of tumors.
Suramin Toxicity and Efficacy in Agnogenic Myeloid Metaplasia
Authors: A. Tefferi, M. N. Silverstein, E. A. Plumhoff, J. M. Reid, M. M. Ames
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Suramin Toxicity and Efficacy in Agnogenic Myeloid Metaplasia Get access Ayalew Tefferi, Ayalew Tefferi Division of Hematology and Internal Medicine, Mayo Clinic and Mayo FoundationRochester, Minn Correspondence to : Ayalew Teffen, M.D., Mayo Clinic, 200 First Street SW, Rochester, MN 55905 Search for other works by this author on: Oxford Academic PubMed Google Scholar Murray N. Silverstein, Murray N. Silverstein Division of Hematology and Internal Medicine, Mayo Clinic and Mayo FoundationRochester, Minn Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth A. Plumhoff, Elizabeth A. Plumhoff Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo FoundationRochester, Minn Search for other works by this author on: Oxford Academic PubMed Google Scholar Joel M. Reid, Joel M. Reid Division of Developmental Oncology Research, Mayo Clinic and Mayo FoundationRochester, Minn Search for other works by this author on: Oxford Academic PubMed Google Scholar Matthew M. Ames Matthew M. Ames Division of Developmental Oncology Research, Mayo Clinic and Mayo FoundationRochester, Minn * See “Notes” section following “References.” Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 18, 15 September 1993, Pages 1520–1522, https://doi.org/10.1093/jnci/85.18.1520 Published: 15 September 1993 Article history Received: 04 March 1993 Revision received: 11 May 1993 Accepted: 07 July 1993 Published: 15 September 1993
OP0210 TLR-2 Induces Pro-Inflammatory/Angiogenic Mechanisms in GCA Temporal Artery Explant Cultures Ex Vivo
Authors: A. Maher, D. Molloy, J. McCormick, L. O’Neill, D. Veale, C. Murphy, U. Fearon, E. Molloy
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Giant cell arteritis (GCA) is a common form of primary vasculitis characterised by dysfunctional vessels and inflammatory infiltration leading to luminal occlusion. Toll-Like receptor-2 (TLR2) has been implicated in the pathogenesis of GCA; however, the mechanisms involved have yet to be elucidated. <h3>Objectives</h3> This study examines the mechanistic role of TLR2 activation in regulating the pro-inflammatory mechanisms in GCA. <h3>Methods</h3> Temporal artery (TA) sections from patients positive and negative for GCA were assessed for TLR2 expression by immunohistology. <i>Ex-vivo</i> TA explant cultures were stimulated with Pam3CSK4 (TLR2 agonist) (1ug/ml) for 24 hrs. VEGF, Ang2, IL-6, IL-8 and MMP2/9 expression was quantified in cultured supernatants by ELISA and gelatin zymography. The effect of Pam3CSK4-induced GCA TA explant conditioned media on endothelial cell (dHMVEC) function was assessed by angiogenic assays. GCA TA explant myofibroblast outgrowth was assessed using matrigel assays (1-20 days)<sup>1</sup>. Finally the effect of GCA TA explant conditioned media on Human embryonic kidney (HEK)-TLR2 cells was quantified by NFκB luciferase reporter assays. <h3>Results</h3> TLR2 expression was higher in positive versus negative TA sections. Pam3CSK4 significantly increased VEGF, IL-6 and IL-8 expression (all p&lt;.0.05), with differential effects observed for Ang2 and MMP2/9 in TA explant cultures. Pam3CSK4-induced GCA TA conditioned media promoted dHMVEC tube formation (p&lt;0.05). Pam3CSK4 induced myofibroblast outgrowths from GCA TA explants embedded in matrigel. Finally GCA TA conditioned media induced TLR2 activation through induction of NF-κB activation in HEK-TLR2 cells (p&lt;0.05), confirming the presence of endogenous ligands for TLR2 at the site of inflammation in GCA. <h3>Conclusions</h3> Using <i>ex-vivo</i> TA explant cultures, TLR2 activation induced angiogenic and invasive functional mechanisms in GCA. Furthermore activation of TLR2 by GCA TA conditioned media, suggests that TLR2 may represent a potential therapeutic target for GCA. <h3>References</h3> Lozano E, Segarra M, García-Matínez A, Hernández-Rodríguez J, Cid MC. (2008) Imatinib mesylate inhibits in vitro and ex vivo biological responses related to vascular occlusion in giant cell arteritis. Ann Rheum Dis., 67(11): 1581-8. <h3>Disclosure of Interest</h3> A. Maher: None Declared, D. Molloy: None Declared, J. McCormick: None Declared, L. O'Neill: None Declared, D. Veale Grant/research support from: Abbott, Opsona, Pfizer, Roche, Consultant for: MSD, Pfizer, Roche, Speakers bureau: Janssen, MSD, Pfizer, UCB, C. Murphy: None Declared, U. Fearon: None Declared, E. Molloy: None Declared
Metronidazole to Prevent Preterm Delivery in Pregnant Women with Asymptomatic Bacterial Vaginosis
Authors: J. Christopher Carey, Mark A. Klebanoff, John C. Hauth, Sharon L. Hillier, Elizabeth A. Thom, J.M. Ernest, R. Phillip Heine, Robert P. Nugent, Molly L. Fischer, Kenneth J. Leveno, Ronald Wapner, Michael Varner, Wayne Trout, Atef Moawad, Baha M. Sibai, Menachem Miodovnik, Mitchell Dombrowski, Mary J. O'Sullivan, J. Peter VanDorsten, Oded Langer, James Roberts
Journal: New England Journal of Medicine (2000)

Bacterial vaginosis has been associated with preterm birth. In clinical trials, the treatment of bacterial vaginosis in pregnant women who previously had a preterm delivery reduced the risk of recurrence.
BIOMARKER PROFILES IN HEART FAILURE PATIENTS WITH A PRESERVED AND REDUCED EJECTION FRACTION
Authors: Jasper Tromp, IJsbrand Klip, Sven Meyer, Rudolf De Boer, Tiny Jaarsma, Hans Hillege, Dirk van Veldhuisen, Adriaan Voors, Peter Vandermeer
Journal: Journal of the American College of Cardiology (2015)
Abstract SY35-01: Clonal evolution of pre-leukemic hematopoietic stem cells precedes human acute myeloid leukemia
Authors: Max Jan, Thomas Snyder, M. Ryan Corces-Zimmerman, Stephen Quake, Irving Weissman, Ravindra Majeti
Journal: Cancer Research (2012)

Abstract Acute myeloid leukemia (AML) is an aggressive malignancy of hematopoietic progenitors with poor clinical outcomes. Despite the power of next-generation genome sequencing to describe AML genomes and to identify recurrent mutations, our fundamental understanding of both the genomics of leukemogenesis and the genetic heterogeneity within the precursor cells is incomplete. Founding mutations in the majority of AML cases are largely unknown because pre-leukemic cells are clinically silent and are outcompeted by their malignant descendants. Our limited knowledge of founding mutations comes from infrequent cases of AML arising secondary to antecedent clonal bone marrow disorders or rare instances of inherited syndromes, but this does not include the large majority of de novo AML cases. Recently, advances in AML stem cell biology have enabled the prospective separation of residual hematopoietic stem cells (HSC) from AML cells. We previously showed that residual HSC contain clonal antecedents of AML in patients in long-term remission post-therapy, and have proposed a model in which serial acquisition of mutations occurs in self-renewing HSC. Here, we investigated this model and the nature of founder mutations through the genomic analysis of de novo AML and patient-matched residual HSC. Using exome sequencing, we defined mutations present in individual AML genomes from cases harboring the FLT3-ITD mutation, and screened for these mutations in the residual HSC. We identified several mutations present in residual HSC retaining normal multilineage differentiation in vivo, including mutations in NPM1, TET2, and SMC1A, a newly identified recurrently mutated gene in AML. Finally, through single cell analysis, we determined that as we hypothesized, a clonal progression of multiple mutations occurs in HSC. These pre-leukemic HSC reveal the clonal evolution of AML genomes from founder mutations, suggest a potential mechanism contributing to relapse, and constitute a cellular reservoir that may need to be targeted for more durable remissions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY35-01. doi:1538-7445.AM2012-SY35-01
SAT0280 Prolonged Risk of Specific Malignancies following Cyclophosphamide-Therapy among Patients with Granulomatosis with Polyangiitis (WEGENER'S)
Authors: M. Faurschou, L. Mellemkjaer, A. Voss, K.K. Keller, I.T. Hansen, B. Baslund
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The long-term cancer-risk of patients treated for granulomatosis with polyangiitis (Wegener9s; GPA) is not well characterized. <h3>Objectives</h3> We assessed the risk of early and late-occurring cancers among 293 patients diagnosed with GPA during 1973-1999 and followed throughout 2010. <h3>Methods</h3> The cancer-incidence in the cohort was determined by linkage with the Danish Cancer Registry and compared to that in the general population by calculation of standardized incidence ratios (SIRs). <h3>Results</h3> The median duration of follow-up was 9.7 (range: 0-36) years. 73 cancers occurred, of which 30 were non-melanoma skin cancers (NMSC) and 11 were bladder carcinomas. A high occurrence of NMSC was observed from the second year of follow-up onwards, with a SIR of 7.0 (95% CI: 2.3-16) for cases diagnosed ≥20 years after GPA. The incidence of bladder cancer was increased after 5-9, 10-14, and 15-19 years of follow-up, with SIR estimates for these latency-periods of 5.3 (95% CI: 1.1-15), 14.4 (95% CI: 5.3-31), and 10.5 (95% CI: 1.2-38), respectively. The incidence of myeloid leukemia was significantly increased during year 5-9 (SIR: 23.9 (95% CI: 2.7-86)). Increased incidence of NMSC, bladder cancer, and myeloid leukemia was observed among patients exposed to cumulative cyclophosphamide-doses &gt;36 gram, while the only malignancy-type observed in excess among those treated with lower cyclophosphamide-doses was NMSC. The cancer-risk among cyclophosphamide-naïve patients was not significantly increased. <h3>Conclusions</h3> GPA patients experience a greater-than-expected number of cancers following conventional therapies, including an increased number of very late-occurring malignancies. The risk of specific cancer-types rises with the cumulative cyclophosphamide-dose administered. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5439
Methylation Status of Promoters 0K, 0N and a Newly Identified Promoter Regulate ERβ1 Expression in Breast Cancer.
Authors: H. Al-Nakhle, L. Smith, T. Hughes, M. Cummings, A. Hanby, A. Shaaban, P. Burns, V. Speirs
Journal: Cancer Research (2009)

Abstract Gene expression is regulated at multiple levels, including transcriptional silencing by methylation. ERβ1 is downregulated in breast cancer compared to normal breast and mechanisms surrounding this are unclear. Two novel ERβ mRNA isoforms with distinct 5'-UTRs have been identified, ERβ-0K-1 and ERβ-0N-1. The aim of study was to examine whether methylation at these promoter regions plus a novel promoter identified by our group were involved in ERβ1 regulation (figure 1).Bisulfite modification and direct sequencing analysis were performed for promoters 0K, 0N, and a novel mini CpG island upstream of ERβ exon1 in two ERβ1- and one ERβ1+ breast cancer cell lines. Distinct methylation patterns were observed. Promoter 0N was completely methylated in BT20, partially methylated in MDAMB453 and unmethylated in T47D, while the mini CpG island was methylated in all 3 cell lines. In contrast, promoter 0K was unmethylated. Furthermore, a negative correlation between ERβ1 mRNA expression and the methylation status of promoter 0N was observed in breast cells. To further investigate whether methylation of the ERβ1 promoter was responsible for the loss of ERβ1 expression, BT20 and MDAMB453 cells were treated with either 5-aza-dC, TSA or both, concentrations of which had been previously optimised for each cell line. In BT20 cells which had complete methylation of 0N, both agents were required for induction of ERβ1 and ERβ-0N-1 but not ERβ-0K-1 expression, both of which are part of the 5'UTR region. However in MDAMB453 treatment with 5-aza-dC was sufficient to induce ERβ1 and ERβ-0N-1 expression with no additional re-expression seen with TSA and no effects on ERβ-0K-1. This suggests that promoter 0N is responsible for driving the transcription of ERβ1. On going work is confirming these observations in clinical samples. Our results suggest that promoter 0N plays an important role in regulation of ERβ1 mRNA expression in breast cancer. Our results add to growing literatures which demonstrate ERβ1 is regulated at multiple levels in breast cancer and that DNA methylation is an important mechanism for silencing ERβ1 gene expression. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1148.