tbuckley/cabot-search huggingface dataset:
Abstract 1449: A loss-of-function shRNA library screen for the cell invasion-suppressing genes in LNCaP prostate cancer cells
Authors: Bing Su, Catherine Baranowski, Irwin H. Gelman
Journal: Cancer Research (2011)

Abstract Metastasis remains the primary cause of cancer-related death. Metastasis reduces the 5-year survival rate dramatically, as observed in prostate cancer, and yet, little is known about the genes that control the metastatic process. shRNA libraries are emerging as powerful tools for the identification of genes with specific functions. Here, we describe the successful application of this functional gene-discovery system by identifying genes suppressing tumor invasion, a process that is essential for metastasis. After infecting human prostate cancer cells, LNCaP, with Decode lentiviruses encoding the entire human genomic shRNA library, highly invasive variants were selected using Matrigel invasion assays. After three cycles of selection, we isolated highly invasive clones from 7 shRNA library pools. Using DNA sequence analysis and a database search, we identified five genes previously not associated with control of tumor cell invasiveness: forkhead box O4 (FOXO4), kinesin family member 3B (KIF 3B), signal transducing adaptor molecule (SH3 domain and ITAM motif) 1 (STAM), SUMO1/sentrin specific peptidase 1 (SENP1), and Homo sapiens solute carrier family 17 (SLC17A4). Silencing of FOXO4, a member of Forkhead transcription factors family, by small interfering RNAs indeed increased invasion of LNCaP cells. Reintroducing FOXO4 decreased invasion in the highly invasive prostate cancer cell lines DU145 and CWR22v1. In order to show that increased invasiveness was not a result of a change in survival ability, apoptosis and proliferation were assessed. The results indicate that FOXO4 did not affect proliferation and apoptosis in LNCaP cells. In mammals, the FOXO family comprises four members (FOXO1, FOXO3, FOXO4 and FOXO6). Though FOXO1, 3 and 4 have previously been described as having redundant functions, it appears that FOXO4 has unique metastasis suppressor function in prostate cancer. Additionally, an analysis of web-based gene expression databanks indicates that FOXO4 typically is downregulated in metastatic lesions of breast, prostate and colon cancers when compared to primary lesions. Further characterization of these candidate genes would clarify the complex mechanisms of invasion and metastasis and might reveal new classes of therapeutic targets distinct from known metastatic genes. 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 1449. doi:10.1158/1538-7445.AM2011-1449
Antenatal Treatment of Neonatal Alloimmune Thrombocytopenia
Authors: James B. Bussel, Richard L. Berkowitz, Janice G. McFarland, Lauren Lynch, Usha Chitkara
Journal: New England Journal of Medicine (1988)

Neonatal alloimmune thrombocytopenia results from the formation of a maternal antibody to a paternal antigen on fetal platelets. Intracranial hemorrhage, which may be antenatal, occurs in approximately 15 to 20 percent of infants with this form of thrombocytopenia. In families with an affected infant, 75 percent of subsequent infants are affected. We report the results of antenatal treatment with intravenous gamma globulin, with or without dexamethasone, in seven pregnant women who had previously had infants who had severe alloimmune thrombocytopenia. The platelet count increased by a mean (+/- SD) of 72.5 +/- 62 x 10(9) per liter in the six fetuses in whom periumbilical blood sampling was performed. All seven treated fetuses had platelet counts above 30 x 10(9) at birth, and none had an intracranial hemorrhage, in contrast to all seven of their respective untreated siblings, who had lower platelet counts and three of whom had intracranial hemorrhages (antenatal in two infants). Mild intrauterine growth retardation was observed in one treated infant; all seven infants have developed normally in the two months to four years since birth. We conclude that intravenous gamma globulin, with or without dexamethasone, is effective in elevating the fetal platelet count in severe cases of neonatal alloimmune thrombocytopenia and in helping to avoid intracranial hemorrhage.
Drug-Induced Illness
Authors: C. Joseph Stetler
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Talley and Laventurier stated that their earlier estimate of 30,000 deaths annually in the United States due to adverse drug reactions (ADRs) was too low, and that on the basis of new evidence, the number of such deaths ranges from 60,000 to 140,000 annually. The matter is of particular concern to the prescription drug industry since it has been suggested that companies, through overpromotion, are responsible for these deaths and hospital admissions. An attempt to trace the history of the 30,000 ADR death estimate, to review the pertinent literature, and to substantiate the 3,000 to 6,000 estimate follows. The issue has two parts: How many deaths occur annually because of adverse drug reactions, and to what extent can they be attributed to "promotional activities of the drug industry"? <h3>Background.—</h3> The history of the 30,000 statistic is convoluted. In a paper presented in August 1972 at Sea Island,
Trimethoprim-Sulfamethoxazole Prophylaxis of Spontaneous Bacterial Peritonitis
Authors: Sergio de A. Nishioka
Journal: Annals of Internal Medicine (1995)

Letters15 November 1995Trimethoprim-Sulfamethoxazole Prophylaxis of Spontaneous Bacterial PeritonitisSergio de A. Nishioka, MD, MScSergio de A. Nishioka, MD, MScUniversidade Federal de Uberlandia; Uberlandia, Minis Gerais; BrazilSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-10-199511150-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Singh and colleagues [1] reported that trimethoprim-sulfamethoxazole was effective for preventing spontaneous peritonitis in patients with cirrhosis. They also argued that this drug has a lower cost and fewer associations with selection of gram-positive bacteria than norfloxacin. Although I agree with their arguments, their results may lead to a different conclusion regarding the efficacy of prophylactic trimethoprim-sulfamethoxazole. Their results appear impressive; 8 of 30 controls and 1 of 30 patients receiving prophylaxis developed spontaneous peritonitis or spontaneous bacteremia. However, two controls had enterococcal peritonitis, and one had Klebsiella pneumoniae bacteremia, conditions that one would not expect to ...REFERENCE1. Singh N, Gayowski T, Yu VL, Wagener MM. Trimethoprim-sulfame-thoxazole for the prevention of spontaneous bacterial peritonitis in cirrhosis. A randomized trial. Ann Intern Med. 1995; 122:595-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: Universidade Federal de Uberlandia; Uberlandia, Minis Gerais; Brazil PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 November 1995Volume 123, Issue 10Page: 810KeywordsBacteremiaChemopreventionCirrhosisEnterococcus infectionsGram positive bacteriaKlebsiellaKlebsiella pneumoniaePeritonitisProphylaxisSpontaneous bacterial peritonitis ePublished: 15 August 2000 Issue Published: 15 November 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Nucleotide-sugar transporter SLC35D1 is critical to chondroitin sulfate synthesis in cartilage and skeletal development in mouse and human
Authors: Shuichi Hiraoka, Tatsuya Furuichi, Gen Nishimura, Shunichi Shibata, Masaki Yanagishita, David L Rimoin, Andrea Superti-Furga, Peter G Nikkels, Minako Ogawa, Kayoko Katsuyama, Hidenao Toyoda, Akiko Kinoshita-Toyoda, Nobuhiro Ishida, Kyoichi Isono, Yutaka Sanai, Daniel H Cohn, Haruhiko Koseki, Shiro Ikegawa
Journal: Nature Medicine (2007)
Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation
Authors: G. Palladini
Journal: Blood (2003)

The most efficient therapeutic approach for immunoglobulin light chain amyloidosis (AL) is autologous stem cell transplantation (ASCT); however, the toxicity of ASCT limits its feasibility to a minority of patients. Patients ineligible for ASCT are usually treated with standard oral melphalan and prednisone, but the response rate to this regimen is unsatisfactory, and time to response is long. High-dose dexamethasone provides a rapid response time in patients with AL. We evaluated the combination of oral melphalan and high-dose dexamethasone (M-Dex) in 46 patients with AL ineligible for ASCT. Thirty-one (67%) achieved a hematologic response and 15 (33%) a complete remission. In 22 (48%) of the responsive patients functional improvement of the organs involved was observed. Five patients (11%) experienced severe adverse events, 3 required hospitalization, and no treatment-related deaths were observed. M-Dex represents a feasible and effective therapeutic option for patients with advanced AL who are ineligible for ASCT.
Effects of Pulmonary Insufficiency on Biventricular Function in the Developing Heart of Growing Swine
Authors: Titus Kuehne, Maythem Saeed, Kelly Gleason, Daniel Turner, David Teitel, Charles B. Higgins, Phillip Moore
Journal: Circulation (2003)

This study was conducted to determine the effects of chronic pulmonary insufficiency (PI) on right (RV) and left (LV) ventricular function in young growing swine.Six PI and 5 control animals were studied. PI was induced by transcatheter placement of stents across the pulmonary valve. Indices of systolic function (ejection fraction, cardiac output, and cardiac functional reserve), diastolic function (compliance), and myocardial contractility (the slope of the relationship of end-systolic pressure versus end-systolic volume [Emax] and the slope of the dP/dtmax-end-diastolic volume relationship [MdP/dt]) were assessed within 2 days of intervention and 3 months later. MRI was used to quantify PI and ventricular volumes. Conductance catheter techniques were used to obtain indices of contractility and diastolic compliance from pressure-volume relations at rest and under dobutamine infusion. In the PI group, pulmonary regurgitant fraction was 49.2+/-5.9% at 3-month follow-up. RV cardiac functional reserve was limited, diastolic function was preserved, and myocardial contractility was altered (Emax=2.6+/-0.3 mm Hg/mL for the PI group versus 3.5+/-0.4 mm Hg/mL for control; P<0.01). LV cardiac functional reserve was limited, ventricular compliance decreased, and myocardial contractility was preserved.In the young developing heart, chronic PI alters biventricular systolic function, RV myocardial contractility, and LV diastolic performance.
Portable Anaesthetic Apparatus
Authors: T. H. S. Burns
Journal: BMJ (1965)

zine), with which she was being treated, the oedema recurred at irregular intervals.The fourth case was a girl aged 21 under the care of St. Thomas's Hospital, who was on Tofranil (imipramine), Marsilid (iproniazid), and Largactil (chlorpromazine).Her mother had charge of the tablets.She was admitted to hospital in coma.Blood and urine samples showed no evidence of drug overdosage.When she recovered she denied to hospital staff that she had taken anything other than the normal dose.The mother confirmed this.Yet, after discharge from hospital, the girl told us that for weeks she had been palming the nightly chlorpromazine tablet, and had taken 40 tablets before lapsing into coma.We have at this time over 50 patients on various antidepressants, and though some of them can hardly stand up because of hypotensive effects they are all finding life worth living.It is the family doctor who should be pre- scribing these drugs, certainly singly, and it is hoped, as we gain more experience, in combination.It is the writing of physicians, pathologists, toxicologists, and committees with little clinical experience of handling the antidepressants that is making it difficult for Us to accept the much more authoritative statements of those who think, teach, and practise as Dr. Sargant does.Our patients do not die from antidepressant drugs, either singly, in combination, or in massive overdosage.They sometimes die by their own hands without them.-Iam, etc., London S.W.11.B. HYNES.And-folic-acid Drugs SIR,-In " To-day's Drugs" (30 January, p. 302) your expert says, with respect to antifolics, " The effect these substances have on the germinal chromosomes is unknown, but may be harmful, and they certainly should not be given to women in the child-bearing age."Are we to deduce from the above that anti- folics can safely be given to men in their procreative years ?-Iam, etc.,
Idiopathic pneumonia syndrome after hematopoietic cell transplantation: evidence of occult infectious etiologies
Authors: Sachiko Seo, Christian Renaud, Jane M. Kuypers, Charles Y. Chiu, Meei-Li Huang, Erik Samayoa, Hu Xie, Guixia Yu, Cynthia E. Fisher, Ted A. Gooley, Steven Miller, Robert C. Hackman, David Myerson, Ruth H. Sedlak, Yae-Jean Kim, Takahiro Fukuda, David N. Fredricks, David K. Madtes, Keith R. Jerome, Michael Boeckh
Journal: Blood (2015)
Lamivudine/interferon combination therapy prevents the appearance of YMDD mutants in anti-HBE positive chronic hepatitis B: A controlled pilot study
Authors: M. Levrero, G. Stivali, A. Rossini, F. Soccorsi, R. Paffetti, I. Gallo, M.E. Bonaventura, G. Bombardieri, G.C. Iaiani, C. Balsano
Journal: Journal of Hepatology (2003)
Intrahepatic mast cells in chronic liver diseases*1
Authors: D FARRELL
Journal: Hepatology (1995)

Mast cells are known to be present in human liver but their distribution and density in normal livers and in chronic liver diseases have not previously been examined. In this study, we quantified mast cell numbers and examined their distribution in percutaneous biopsy specimens from normal livers (n = 8) and in two chronic progressive liver diseases: primary biliary cirrhosis (PBC) (n = 40) and alcoholic liver disease (n = 33). We compared differences in mast cell density between these two forms of chronic liver disease because it had been suggested that mast cells may play a role in the development of liver fibrosis, particularly in patients with chronic cholestatic liver disease who frequently have increased plasma histamine levels. Mast cells were identified by immunohistochemistry using a specific monoclonal antibody (AA1) raised against mast cell tryptase after an initial study showed this to be more sensitive for the detection of mast cells than the conventional histochemical stain, toluidine blue. Our results showed that small numbers of mast cells (3.9 +/- 3.3/mm2) are present within the portal tracts and sinusoids of normal livers. In progressive chronic liver disease, increased numbers of mast cells were present, which correlated with the increasing amounts of liver fibrosis present. We found significantly more mast cells in the PBC group compared with the alcoholic group for a given amount of fibrosis. Our findings suggest that mast cells and their mediators may play a role in liver fibrogenesis.
Ministers are criticised after plans for plain pack cigarettes are put on hold
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Cancer Research UK has said it is “bitterly disappointed” by the government’s decision to wait for more evidence on the effects of standardised plain packaging on cigarette and other tobacco products before deciding whether to adopt the policy.

The charity said that branding on cigarette packets made them more attractive to children, with around 40% of regular smokers saying they started smoking before the age of 16.

Harpal Kumar, the charity’s chief executive, said that lives would be lost as a result of the decision and accused the government of putting industry profits ahead of children’s health.

He added, “What’s shocking is that more than 200 000 children start smoking every year in the [United Kingdom]. They are lured into an addiction that is often lifelong but that kills half of all long term users. We can’t stand …
Alexandra Tobert (née Noskwith)
Authors: Jonathan Tobert, Patricia Vicary
Journal: BMJ (2004)

Former practitioner of psychosexual medicine Nottingham (b Chemnitz, Germany, 1921;q Royal Free Hospital, London, 1944), d 27 June 2004.

Alexandra Tobert was a medical student and house officer in London during the Blitz, surviving a bomb hit on the Royal Free Hospital in 1944. From working in family planning and marriage guidance clinics, she developed an interest in psychosexual medicine. Alexandra worked in private practice and at the Psychosexual Problem Clinic, Nottingham Health District, Nottingham. After retirement she joined Victim Support and helped victims of sexual assault and other crimes. She died from a dementing illness and bronchopneumonia 12 hours after the death of her husband, Gerald. She leaves four children and 10 grandchildren.
Denotation of Dyspnea
Authors: E. D. Morton
Journal: JAMA (1978)

<h3>To the Editor.—</h3> The use of the word "dyspnea" by Thomas A. Raffin, MD, and James Theodore, MD, in their discussion in CLINICAL CARDIOLOGY "Separating Cardiac From Pulmonary Dyspnea" (238:2066, 1977), disturbed me. They carefully defined the word as "an uncomfortable awareness of the act of breathing, leading to a sensation most conveniently described as breathlessness." They then used the word in an objective sense, using the adjectives "cardiac" and "pulmonary" in describing types of dyspnea. It would seem that dyspnea, although having many causes, would still be (according to their definition) only a feeling of breathlessness. Dyspnea—the subjective dyspnea—is still only a sensation, whether it is caused by a garrotte or an elevated CO<sub>2</sub>content of the blood. However, it is not my intention to be contentious about the definition. It may be that I am even more confused than the authors of the article. For 25 years
The applicability of hepatocellular carcinoma risk prediction scores in a North American patient population with chronic hepatitis B infection
Authors: Mahmoud Abu-Amara, Orlando Cerocchi, Gurtej Malhi, Suraj Sharma, Colina Yim, Hemant Shah, David K Wong, Harry L A Janssen, Jordan J Feld
Journal: Gut (2015)

Patients with chronic hepatitis B (CHB) infection are at an increased risk of developing hepatocellular carcinoma (HCC). Risk scores have been developed in Asian populations to predict HCC risk over time.To assess the performance of HCC risk prediction models in a heterogeneous population of patients with CHB.Scores were calculated at baseline using CU-HCC, REACH-B, NGM1-HCC, NGM2-HCC and GAG-HCC models and the incidence of HCC was determined. The predictive ability of each score was evaluated using the area under the receiver operating characteristic curve (AUROC), Cox regression and plots of observed versus predicted HCC. The predictive value of the scores was compared between Asian and non-Asian patients and between cirrhotic versus non-cirrhotic with and without treatment.Of 2105 patients, 70 developed HCC. Increasing risk score was associated with HCC in all models. The CU-HCC model had the highest AUROC in Asian (0.85) and non-Asian (0.91) patients. Patients identified as low risk by any model had a very low incidence of HCC (0-0.15 per year), with the highest proportion of patients identified as low risk using CU-HCC (67%) or GAG-HCC (78%). The risk of HCC was similar to predicted for low-risk and medium-risk patients but was lower than predicted for high-risk patients. Treated patients had a lower than predicted risk of HCC, particularly in non-cirrhotic high-risk patients with longer follow-up.Although all models predicted the risk of HCC, models that incorporated parameters of liver function or cirrhosis (CU-HCC/GAG-HCC) were most accurate. Low-risk patients likely require reduced HCC surveillance.
Lipoprotein(a). Clinical approach to a unique atherogenic lipoprotein
Authors: D. J. Rader
Journal: JAMA (1992)

<h3>SELECTED CASE</h3> A 42-YEAR-OLD man was referred because of premature coronary artery disease (CAD). He had been healthy until 3 months earlier, when he sustained a non—Q wave myocardial infarction. Cardiac catheterization revealed severe triple-vessel coronary disease, and he underwent coronary artery bypass grafting. He was not a smoker and had no history of diabetes mellitus or hypertension. Family history was remarkable for a father who died of an acute myocardial infarction at the age of 54 years. Three weeks after surgery, a random serum cholesterol level was 5.38 mmol/L. Physical examination of the patient at the National Institutes of Health revealed no corneal arcus, normal liver and spleen size, and no evidence of palmar, tuberoeruptive, or tendon xanthomas. Laboratory values included a normal fasting blood glucose, normal serum urea nitrogen, and normal serum tests of liver and thyroid function. Fasting plasma lipid and lipoprotein values included the following: triglycerides,
Adenosine increases lactate release and delays onset of contracture during global low flow ischaemia
Authors: R. D Lasley, R. M Mentzer
Journal: Cardiovascular Research (1993)

Adenosine reduces myocardial ischaemic injury and enhances postischaemic recovery of function following zero flow global and regional ischaemia. The purpose of this study was to determine the functional and metabolic effects of endogenous and exogenous adenosine during low flow ischaemia.Isolated perfused rat hearts (n = 80), paced at 300 beats-min-1, were subjected to 45 min of low flow ischaemia (0.6 ml.min-1). The time to onset of ischaemic contracture (TOIC) was used as a marker of myocardial ischaemic injury. Coronary venous effluent samples were collected prior to and throughout ischaemia to measure lactate and purine release. Untreated hearts were compared to hearts treated with either adenosine (100 microM), adenosine plus EHNA (erythro-9-[2-hydroxy-3-nonyl]adenine HCl), an adenosine deaminase inhibitor (50 microM), or BW A1433U, an adenosine receptor blocker (5 microM).Adenosine and adenosine+EHNA prolonged TOIC from 11.6 (SEM 0.5) min to 13.6(0.5) and 13.5(0.3) min, respectively, and increased lactate release from 1.67(0.19) mumol.min-1.g-1 to 2.20(0.09) and 2.35(0.31) mumol.min-1.g-1, respectively, after 20 min ischaemia. Treatment with BW A1433U reduced TOIC [8.7(0.2)min] and markedly reduced lactate release. When glucose was omitted from the perfusate, adenosine+EHNA treatment had no effect on TOIC. Lactate release during glucose free perfusion was similar to that in hearts treated with the adenosine receptor blocker.Endogenous and exogenous adenosine may enhance myocardial tolerance to ischaemia in part via the modulation of glucose metabolism.
Impact of dietary fat quantity and quality on skeletal muscle fatty acid metabolism in subjects with the metabolic syndrome
Authors: Anneke Jans, Anneke M.J. van Hees, Ingrid M.F. Gjelstad, Lauren M. Sparks, Audrey C. Tierney, Ulf Risérus, Christian A. Drevon, Patrick Schrauwen, Helen M. Roche, Ellen E. Blaak
Journal: Metabolism (2012)