tbuckley/cabot-search huggingface dataset:
Abstract 5450: Screening more than 60 human SCLC lines with approved and investigational agents indicates complex patterns of response: Identification of HSP90 and HDACs as potential targets
Authors: David M. Evans, Rene Delosh, Julie Laudeman, Chad Ogle, Russell Reinhart, Michael Selby, Thomas Silvers, John Connelly, Anne Monks, Eric Polley, Gurmeet Kaur, Joel Morris, Beverly Teicher
Journal: Cancer Research (2014)

Abstract Small cell lung cancer (SCLC) is an aggressive cancer with a 5-year survival rate of &amp;lt;5%. While initially responsive to treatments with platinum agents, topoisomerase inhibitors or methotrexate, the tumors frequently recur after chemotherapy. To identify whether approved small molecule drugs or investigational agents may have unexpected effects in SCLC lines, we undertook a systematic large-scale screen with &amp;gt;500 compounds against &amp;gt; 60 well characterized SCLC cell lines in culture. Cells were exposed to 101 Approved Oncology Drugs (AOD) and 433 Investigational Agents. By evaluating compounds at 9 concentrations (10uM to 1.5nM), using cell viability 96h post drug exposure as the endpoint (Cell Titer Glo), we were able to obtain concentration response curves and IC50 values for the compounds and rank activity of these agents. In parallel studies, using Affymetrix exon ST1 arrays and miRNA profiling, we examined these same cell lines for differences in gene expression patterns that may correlate with sensitivity or resistance to select agents in the screen. The Myc oncogene (cMyc, LMyc, or nMyc) is over-expressed in about 40% of SCLC lines. Surprisingly, early analyses of the SCLC screen data have been unable to correlate high Myc expression with response to drugs or investigational agents (there is a trend with bromodomain inhibitors). The large majority of SCLC lines were sensitive to compounds against select target classes (e.g. HSP90 inhibitors and HDAC inhibitors). Examining HSP70 and HSP90 levels by Western blot suggested a slight reduction in HSP90 levels in cells resistant to the HSP90 inhibitor Ganetespib with no change in HSP70 levels. Some inhibitors against these targets showed broader cell activity than others. We are currently determining whether such differential drug sensitivity is correlated with specific changes in gene expression patterns in these cells. Further data analyses from the screen combined with genomic profiling of the cells will be presented. Funded by NCI Contract No. HHSN261200800001E. Citation Format: David M. Evans, Rene Delosh, Julie Laudeman, Chad Ogle, Russell Reinhart, Michael Selby, Thomas Silvers, John Connelly, Anne Monks, Eric Polley, Gurmeet Kaur, Joel Morris, Beverly Teicher. Screening more than 60 human SCLC lines with approved and investigational agents indicates complex patterns of response: Identification of HSP90 and HDACs as potential targets. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5450. doi:10.1158/1538-7445.AM2014-5450
Timing and cost of scaling up surgical services in low-income and middle-income countries from 2012 to 2030: a modelling study
Authors: Stéphane Verguet, Blake C Alkire, Stephen W Bickler, Jeremy A Lauer, Tarsicio Uribe-Leitz, George Molina, Thomas G Weiser, Gavin Yamey, Mark G Shrime
Journal: The Lancet Global Health (2015)

BackgroundGiven the large burden of surgical conditions and the crosscutting nature of surgery, scale-up of basic surgical services is crucial to health-system strengthening. The Lancet Commission on Global Surgery proposed that, to meet populations' needs, countries should achieve 5000 major operations per 100 000 population per year. We modelled the possible scale-up of surgical services in 88 low-income and middle-income countries with a population greater than 1 million from 2012 to 2030 at various rates and quantified the associated costs.MethodsMajor surgery includes any intervention within an operating room involving tissue manipulation and anaesthesia. We used estimates for the number of major operations achieved per country annually and the number of operating rooms per region, and data from Mongolia and Mexico for trends in the number of operations. Unit costs included a cost per operation, proxied by caesarean section cost estimates; hospital construction data were used to estimate cost per operating room construction. We determined the year by which each country would achieve the Commission's target. We modelled three scenarios for the scale-up rate: actual rates (5·1% per year) and two "aspirational" rates, the rates achieved by Mongolia (8·9% annual) and Mexico (22·5% annual). We subsequently estimated the associated costs.FindingsAbout half of the 88 countries would achieve the target by 2030 at actual rates of improvements, with up to two-thirds if the rate were increased to Mongolian rates. We estimate the total costs of achieving scale-up at US$300–420 billion (95% UI 190–600 billion) over 2012–30, which represents 4–8% of total annual health expenditures among low-income and lower middle-income countries and 1% among upper middle-income countries.InterpretationScale-up of surgical services will not reach the target of 5000 operations per 100 000 by 2030 in about half of low-income and middle-income countries without increased funding, which countries and the international community must seek to achieve expansion of quality surgical services.FundingNone.
Occupational exposure to petroleum products in men with acute non-lymphocytic leukaemia.
Authors: L Brandt, P G Nilsson, F Mitelman
Journal: BMJ (1978)

was no evidence of spinal arterial thrombosis.The cord showed some degeneration of the medial dorsal columns in keeping with the dorsal root demyelination.There was no evidence of necrosis of the cord or of nerve roots.The findings were thought to be consistent with damage from intrathecal phenol.1977, in press.
Rapid detection of pneumococcal antigen in pleural fluid of patients with community acquired pneumonia.
Authors: W G Boersma, A Lowenberg, Y Holloway, H Kuttschrutter, J A Snijder, G H Koeter
Journal: Thorax (1993)

Detection of pneumococcal antigen may help to increase the rate of diagnosis of pneumococcal pneumonia. This study was designed to determine the value of rapid detection of pneumococcal antigen in pleural fluid from patients with community acquired pneumonia.Thoracentesis was performed in patients suspected of having empyema and in patients with pneumonia of unknown aetiology. Pneumococcal capsular antigen was detected by latex agglutination and this method was compared with Gram staining and culture, specimens of pleural fluid being examined in parallel by the three methods.Pleural fluid was radiographically identified in 63 of 135 patients with community acquired pneumonia. In nine of 45 patients with pneumococcal pneumonia and pleural fluid pneumococci were identified by Gram stain in two and by culture in one specimen of pleural fluid, whereas antigen was detected in eight of these specimens. In 12 of 33 patients with pneumonia of other known aetiology only one pleural fluid specimen was antigen positive, providing a specificity of 92% for this test. Pleural fluid obtained from 12 of 58 patients with pneumonia of unknown aetiology yielded detectable antigen in seven cases.Detection of pneumococcal antigen by latex agglutination in pleural fluid may yield important and rapid information in patients with community acquired pneumonia.
US nurses start "health insurance casualty of the day" website
Authors: J. H. Tanne
Journal: BMJ (2008)

Nurses in the United States are posting daily updates on a website in the lead up to November’s presidential election to highlight the plight of people who can’t get adequate insurance for medical care.

Every day until the 4 November election a “health insurance casualty” medical history is posted on the website of the California Nurses Association and its national arm, the National Nurses Organizing Committee, and emailed to people who have signed up to this service. It …
Modification of β2m with advanced glycation end products as observed in dialysis-related amyloidosis by 3-DG accumulating in uremic serum
Authors: Toshimitsu Niwa, Tomoyuki Katsuzaki, Tomoko Momoi, Takashi Miyazaki, Hiroshi Ogawa, Akira Saito, Shigeru Miyazaki, Kenji Maeda, Noriyuki Tatemichi, Yoshifumi Takei
Journal: Kidney International (1996)
The Bactericidal Action of Light on Tubercle Bacilli
Authors: A. Eidinow
Journal: BMJ (1927)

MZDIJoIBwVINeither stone in the bladder nor gravel, or cystitis, or any abnormalitv of the urinary tract was found at postmortemb examination in any of these 18 animals.CONCirUSION.The addition of whole milk, in the proportion of two- thir(ds of an ounce per rat daily, to a diet capable. of causing urolithiasis in 50 per cent. of young rats, com- pletely prevented the developmnent of phosphatic calculi.
Shadow over Maltese medicine.
Authors: E Grey-Turner
Journal: BMJ (1977)

susceptible to obstruction as a result of lymnphoid hyperplasia until involution of this lymphoid tissue occurs.This relationship would account for the characteristic age distribution of acute appendicitis.On this basis lymphoid hyperplasia occurring during viral exanthemata and bacterial infections could lead to appendicitis.However, one study has shown that there is no greater incidence of acute appendicitis in children with these infections than there is in children who are otherwise well."An alternative explanation is that obstruction is due to muscular spasm in the appendix associated with a low-fibre diet, as is thought to occur in the colon, and this would account for the geographical distribution of the disease.
Nonsense mutation causing steroid 21-hydroxylase deficiency.
Authors: H Globerman, M Amor, K L Parker, M I New, P C White
Journal: Journal of Clinical Investigation (1988)

We determined the sequence of a mutant CYP21B gene isolated from a patient with the severe, "salt-wasting" form of congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. Codon 318 in this gene is changed from CAG, encoding glutamine, to TAG, a nonsense codon. This is predicted to result in a completely nonfunctional enzyme due to premature termination of translation. In addition, when the cloned mutant gene was transfected into mouse Y1 adrenal cells, the resulting mRNA levels were decreased compared with transfected normal CYP21B genes. This mutation was carried by 3 of 20 unrelated patients with 21-hydroxylase deficiency alleles as determined by hybridization with a specific oligonucleotide probe. This mutation is also seen in the normal CYP21A pseudogene, so that its presence in the abnormal CYP21B gene may be the result of a gene conversion event.
Congenital Absence of the Left Pulmonary Artery
Authors: William Bogedain
Journal: JAMA (1962)

Bronchiectasis is a condition which every physician may expect to see in a lifetime. In the present case, however, it coexisted with hemophilia and congenital absence of the left pulmonary artery. Tachycardia, productive cough, dyspnea on exertion, and episodes of pleuritic pain had existed for many years. The patient was 47 years of age when he came to be treated for an acute onset of chills, fever, cough, and pain in his chest. At operation the left lung was found to be polycystic and was removed; at the same time the extensive anomalies of the pulmonary circulation were disclosed. The hemorrhagic tendency was dealt with successfully, and the patient re
Caveolin-1 Deficiency Increases Cerebral Ischemic Injury
Authors: Jean-François Jasmin, Samit Malhotra, Manjeet Singh Dhallu, Isabelle Mercier, Daniel M. Rosenbaum, Michael P. Lisanti
Journal: Circulation Research (2007)

Caveolins (Cav), the principal structural proteins of the caveolar domains, have been implicated in the pathogenesis of ischemic injury. Indeed, changes in caveolin expression and localization have been reported in renal and myocardial ischemia. Genetic ablation of the Cav-1 gene in mice was further shown to increase the extent of ischemic injury in a model of hindlimb ischemia. However, the role of Cav-1 in the pathogenesis of cerebral ischemia remains unknown. Immunoblot and immunofluorescence analyses of rat brains subjected to middle cerebral artery occlusion revealed marked increases in endothelial Cav-1 and Cav-2 protein levels. To directly assess the functional role of caveolins in the pathogenesis of cerebral ischemic injury, we next investigated the effects of cerebral ischemia in caveolin knockout (KO) mice. Interestingly, Cav-1 KO mice showed a marked increase of cerebral volume of infarction, as compared with wild-type and Cav-2 KO mice. Immunofluorescence analyses showed an increased number of proliferating endothelial cells in wild-type ischemic brains, as compared with Cav-1 KO ischemic brains. Immunoblot analyses of wild-type ischemic brains showed an increase in endothelial nitric oxide synthase protein levels. Conversely, the protein levels of endothelial nitric oxide synthase remained unchanged in Cav-1 KO ischemic brains. TUNEL analysis also showed increased apoptotic cell death in Cav-1 KO ischemic brains, as compared with wild-type ischemic brains. Our findings indicate cerebral ischemia induces a marked increase in endothelial Cav-1 and Cav-2 protein levels. Importantly, genetic ablation of the Cav-1 gene in mice results in increased cerebral volume of infarction. Mechanistically, Cav-1 KO ischemic brains showed impaired angiogenesis and increased apoptotic cell death.
Retinoic acid enhances growth of human early erythroid progenitor cells in vitro.
Authors: D Douer, H P Koeffler
Journal: Journal of Clinical Investigation (1982)

We studied the effect of retinoic acid on the clonal proliferation of normal human early erythroid progenitor cells in vitro. Normal peripheral blood cells were cultured in methylcellulose with erythropoietin and the number of burst-forming units-erythroid (BFU-E) colonies were scored on day 12 of culture. All-trans retinoic acid increased the number of colonies in a dose-response fashion. Maximal stimulation occurred at 30 nM retinoic acid, which increased the number of BFU-E by a mean of 225 +/- 25% (+/- SE) over plates containing erythropoietin alone. Colony formation increased even in the presence of maximally stimulating concentrations of erythropoietin. The 13-cis retinoic acid stimulated BFU-E proliferation in a parallel manner as the trans analogue, while retinol (vitamin A) did not affect clonal growth. This data supports further the thesis that retinoic acid, in addition to its known effect on epithelial cells, may be involved in the growth of normal hematopoietic cells.
The Inflammatory Process
Authors: A. E. Rodin
Journal: JAMA (1974)

The stated objectives for this multiauthored work are to make available "an encyclopedic background for research" and to serve as an authoritative reference for graduate and medical students, and experimental biologists. Because immunologic reactions are included under the broad umbrella of host reactions to foreign material, it is not surprising that the second edition has been expanded from one to three volumes. Whereas the first two volumes (not reviewed here) include molecular, cellular, vascular, and hematologic aspects of inflammation, volume 3 is devoted to immunologic and more general aspects. Each chapter can be read as an independent unit. The overall impressions gained from volume 3 are that there have been countless numbers of researchers doing countless numbers of experiments; that many of their observations are isolated and some contradictory; that there are many more suppositions and hypotheses than facts; and that to date only a small percentage of studies can
Franz J. Ingelfinger, 1910–1980
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1980)

Franz Ingelfinger, Editor Emeritus of the Journal, was an indomitable man. He excelled at nearly everything he did, and he managed to reach the top in two professional careers. He even came close to winning his personal struggle with carcinoma of the esophagus. Franz was never a person to give up easily. When he finally died on March 26, at the age of 69, he had survived for more than four years after surgery, far longer than anyone had expected.His extraordinary dual career, first as a distinguished teacher, consultant, and investigator in gastroenterology, and then as editor of . . .
Duodenal Ulcer with Malignant Degeneration
Authors: N. HELLEMANS
Journal: Annals of Internal Medicine (1962)

Case Studies1 August 1962Duodenal Ulcer with Malignant DegenerationN. HELLEMANS, M.D., W. G. R. M. DE BOER, M.D.N. HELLEMANS, M.D.Search for more papers by this author, W. G. R. M. DE BOER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-57-2-295 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMalignant degeneration of a chronic peptic duodenal ulcer is rarely observed, as compared with malignant changes in a peptic ulcer of the stomach. According to Ewing (1), only 10 cases were observed up to 1940. In the same year, Rothaug (2) collected 21 cases of malignant degeneration of duodenal ulcers. On critical evaluation, only 3 cases proved to be adequately documented histologically. These were Rothaug's case of a 74-year-old woman, Ewald's (3) of a woman aged 67, and Kettle's (4) of a man of 68. Pathologists use the same criteria in evaluating such cases as those of malignant degeneration of...References1. EWING J: Neoplastic Diseases, W. B. Saunders Company, Philadelphia, 1942. Google Scholar2. ROTHAUG E: Ueber das Ulcuscarcinom des Duodenums. Frankfurt. Z. Path. 54: 275, 1940. Google Scholar3. EWALD CA: Ein Fall von Atrophie der Magenschleimhaut mit Verlust der Salzsäuresecretion. Berl. Klin. Wschr. 32: 527, 1886. Google Scholar4. KETTLE EH: Malignant change in a chronic duodenal ulcer. Lancet 1: 570, 1930. CrossrefGoogle Scholar5. GEEVERBALTONFAWCETT EFVLNW: Chronic peptic duodenal ulcer with cancerous transformation. Amer. J. Dig. Dis. 18: 61, 1951. CrossrefMedlineGoogle Scholar6. MATEJICEKRYCHLO EA: Ueber das Ulcuscarcinom des duodenums. Zbl. Chir. 79: 2117, 1940. Google Scholar7. BRENNERBROWN RLCH: Primary carcinoma of the duodenum. Report of 15 cases. Gastroenterology 29: 189, 1955. CrossrefMedlineGoogle Scholar8. HINTON JW: Does carcinoma of the duodenum ever arise from duodenal ulcers? Report of cases. Amer. J. Med. Sci. 181: 843, 1931. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Groningen,From the Department of Gastroenterology and the Department of Pathology, University Hospital, Groningen, The Netherlands.Requests for reprints should be addressed to N. Hellemans, M.D., 9 Emmasingel, Groningen,The Netherlands. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByUlcer cancer of the duodenumPeptic Ulcer 1 August 1962Volume 57, Issue 2_Part_1Page: 295-299KeywordsDuodenal ulcersGastric ulcersMucous membranesPancreasPathologistsPeptic ulcersStenosisStomachSurgeonsUlcers Issue Published: 1 August 1962 PDF DownloadLoading ...
RNA-binding protein PCBP2 modulates glioma growth by regulating FHL3
Authors: Wei Han, Zhongshuai Xin, Zhiqiang Zhao, Wen Bao, Xihua Lin, Bin Yin, Jizong Zhao, Jiangang Yuan, Boqin Qiang, Xiaozhong Peng
Journal: Journal of Clinical Investigation (2013)

PCBP2 is a member of the poly(C)-binding protein (PCBP) family, which plays an important role in posttranscriptional and translational regulation by interacting with single-stranded poly(C) motifs in target mRNAs. Several PCBP family members have been reported to be involved in human malignancies. Here, we show that PCBP2 is upregulated in human glioma tissues and cell lines. Knockdown of PCBP2 inhibited glioma growth in vitro and in vivo through inhibition of cell-cycle progression and induction of caspase-3-mediated apoptosis. Thirty-five mRNAs were identified as putative PCBP2 targets/interactors using RIP-ChIP protein-RNA interaction arrays in a human glioma cell line, T98G. Four-and-a-half LIM domain 3 (FHL3) mRNA was downregulated in human gliomas and was identified as a PCBP2 target. Knockdown of PCBP2 enhanced the expression of FHL3 by stabilizing its mRNA. Overexpression of FHL3 attenuated cell growth and induced apoptosis. This study establishes a link between PCBP2 and FHL3 proteins and identifies a new pathway for regulating glioma progression.
Effectiveness of Specialized Palliative Care
Authors: Camilla Zimmermann, Rachel Riechelmann, Monika Krzyzanowska, Gary Rodin, Ian Tannock
Journal: JAMA (2008)

<h3>Context</h3>Specialized palliative care teams are increasingly providing care for the terminally ill. However, the impact of such teams on quality of life, satisfaction with care, and economic cost has not been examined systematically using detailed criteria for study quality.<h3>Objective</h3>To systematically review the evidence for effectiveness of specialized palliative care.<h3>Data Sources</h3>We performed a keyword search of the following databases from their inception to January 2008: MEDLINE, Ovid Healthstar, CINAHL, EMBASE, and the Cochrane Central Register of Controlled Trials.<h3>Study Selection</h3>We included all randomized controlled trials in which specialized palliative care was the intervention and for which outcomes included quality of life, satisfaction with care, or economic cost.<h3>Data Extraction</h3>Data on population, intervention, outcome, methods, and methodological quality were extracted by 2 investigators using standardized criteria.<h3>Results</h3>Of 396 reports of randomized controlled trials, 22 met our inclusion criteria. There was most consistent evidence for effectiveness of specialized palliative care in improvement of family satisfaction with care (7 of 10 studies favored the intervention). Only 4 of 13 studies assessing quality of life and 1 of 14 assessing symptoms showed a significant benefit of the intervention; however, most studies lacked statistical power to report conclusive results, and quality-of-life measures were not specific for terminally ill patients. There was evidence of significant cost savings of specialized palliative care in only 1 of the 7 studies that assessed this outcome. Methodological limitations were identified in all trials, including contamination of the control group, failure to account for clustering in cluster randomization studies, and substantial problems with recruitment, attrition, and adherence.<h3>Conclusions</h3>The evidence for benefit from specialized palliative care is sparse and limited by methodological shortcomings. Carefully planned trials, using a standardized palliative care intervention and measures constructed specifically for this population, are needed.
Chronic lead absorption. Result of poor ventilation in an indoor pistol range
Authors: P. J. Landrigan
Journal: JAMA (1975)

Three cases of mild lead poisoning were discovered among instructors at an indoor pistol range. These cases were characterized by blood lead levels greater than 100 mug/100 ml, free erythrocyte protoporphyrin levels greater than 450 mug/100 ml of red blood cells, abdominal pain, and, in one instance, by slowing of motor and sensory nerve conduction velocity. Exposure to airborne lead produced during revolver-firing and bullet-molding accounted for the lead absorption. Ventilation in the range was inadequate.
Peripheral nerve morphogenesis induced by scaffold micropatterning
Authors: Federica Cerri, Luca Salvatore, Danish Memon, Filippo Martinelli Boneschi, Marta Madaghiele, Paola Brambilla, Ubaldo Del Carro, Carla Taveggia, Nilo Riva, Amelia Trimarco, Ignazio D. Lopez, Giancarlo Comi, Stefano Pluchino, Gianvito Martino, Alessandro Sannino, Angelo Quattrini
Journal: Biomaterials (2014)