tbuckley/cabot-search huggingface dataset:
Abstract 1425: Significance of Dickkopf-3 overexpression in the pathogenesis of esophageal adenocarcinoma
Authors: Zhuwen Wang, Dafydd G. Thomas, Mark B. Orringer, David G. Beer, Jules Lin
Journal: Cancer Research (2011)

Abstract Ninety percent of those diagnosed with esophageal adenocarcinoma ultimately die of their disease highlighting the need for novel therapeutic targets. In order to identify significant molecular changes and potential pathways involved in the progression to esophageal adenocarcinoma, 46 esophagectomy samples, including Barrett's metaplasia, low- and high-grade dysplasia, and esophageal adenocarcinoma, were evaluated using oligonucleotide microarrays. Dickkopf-3 (Dkk-3), a divergent member of the Wnt inhibitor family, was overexpressed in 33.3% (5 of 15) of esophageal adenocarcinoma samples relative to Barrett's metaplasia. The goal of this study was to define the functional significance of Dkk-3 overexpression in esophageal adenocarcinoma. Dkk-3 protein was present at moderate to high levels in 46.8% (29 of 62) of esophageal adenocarcinoma on a tissue microarray. Stable transfection of Dkk-3 into the esophageal adenocarcinoma cell line OE33 lead to significantly increased proliferation 1.6 times vector controls (p &amp;lt; .005). In addition, OE33 cells stably transfected with Dkk-3 showed significantly greater invasion on matrigel assay than native OE33 cells (p &amp;lt; .005). There was no significant decrease in Wnt pathway activation by TOPFLASH assay after transfection of Dkk-3 when compared to OE33 native and vector controls suggesting that overexpression of Dkk-3 acts through a Wnt-independent pathway in esophageal adenocarcinoma. Levels of SMAD4, a key downstream mediator of the TGF-ß pathway, were increased on Western blot after treatment with activin, a member of the TGF-ß superfamily, in OE33 cells stably transfected with Dkk-3 when compared to native and vector controls. These findings suggest that Dkk-3 may be important in mediating proliferation and invasion of esophageal adenocarcinoma through the TGF-β pathway and that Dkk-3 could be a novel therapeutic target in the treatment or prevention of metastatic disease in a cancer with otherwise limited therapeutic options. 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 1425. doi:10.1158/1538-7445.AM2011-1425
Arnold Richard Lyons
Authors: T. J Lyons
Journal: BMJ (2003)

Former physician and radiotherapist Belfast (b Belfast 1917; q Queen's University, Belfast, 1940; MD, FRCP, OBE), died on 26 February 2003 following a subdural haemorrhage.

After qualifying, Arnold Lyons served for five years in the second world war as a medical officer in the Royal Air Force. His acute realisation of the human consequences of aerial bombardment led to a lifelong revulsion towards modern warfare. Following the war and postgraduate study, he cared for patients with cancer, which was to be his main life's work. His interests included photography, painting, writing, and literature. Predeceased by his wife, Doris, he leaves two sons and a grandson.
Reversion of cardiac hypertrophy and reduced arterial compliance after converting enzyme inhibition in essential hypertension.
Authors: R G Asmar, B Pannier, J P Santoni, S Laurent, G M London, B I Levy, M E Safar
Journal: Circulation (1988)

Blood pressure, forearm arterial hemodynamics (with a pulsed Doppler flowmeter), and echocardiographic parameters were studied in 16 patients with sustained essential hypertension before and 3 months after administration of the converting enzyme inhibitor perindopril. In a single-blind study versus placebo, it was shown that perindopril significantly reduced blood pressure (p less than 0.01), whereas there was an increase in brachial blood flow (p less than 0.01) because of a simultaneous increase in blood flow velocity (p less than 0.01) and arterial diameter (p less than 0.01). During a 5-minute period of wrist occlusion, blood flow velocity was reduced to a greater extent with perindopril than with placebo (p less than 0.001), whereas corresponding reductions in arterial diameter were equivalent, indicating that the increase in diameter after perindopril could not be explained simply on the basis of flow-dependent dilatation. During active treatment, brachial artery compliance increased (p less than 0.01) and pulse wave velocity decreased (p less than 0.01), whereas there was no change in the tangential tension of the arterial wall, defined as the product of mean arterial pressure and arterial diameter. Four weeks after treatment was stopped, blood pressure and forearm arterial hemodynamics returned toward baseline values. Cardiac mass was significantly decreased after perindopril (p less than 0.01) and remained decreased 4 weeks after cessation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Response to Letter Regarding Article, “Which Hospitals Have Significantly Better or Worse Than Expected Mortality Rates for Acute Myocardial Infarction Patients? Improved Risk Adjustment With Present-at-Admission Diagnoses”
Authors: George J. Stukenborg, Douglas P. Wagner, M. Norman Oliver, Steven W. Heim, Caroline Kim Han, Andrew M.D. Wolf, Frank E. Harrell, Amy L. Price, Alfred F. Connors
Journal: Circulation (2008)

With Present-at-Admission Diagnoses"We thank Drs Gale, Manda, and Birkhead for their comments and questions regarding our study. 1The variables in our model were derived from California hospital data similar to most US hospital administrative data, except for one difference: California hospitals report which secondary diagnoses were present at admission.The California data included up to 20 ICD-9-CM diagnosis codes for each patient.We grouped the codes into 233 mutually exclusive categories of comorbid disease and included these as dichotomous variables in the model. 2arsimonious models can be advantageous when original data collection is required and resources are limited.However, our study used data routinely collected on discharge from US hospitals.Our aims were to use available hospital data distinguishing which diagnoses are present at admission to develop a valid model that maximally explained and accurately predicted death.We found that substantial additional predictive value is obtained by including adjustments for the large number of conditions that are present at admission, including conditions with small effects on mortality and conditions that occur infrequently.The model that we achieved improved statistical performance and demonstrated external predictive validity in an independent California hospital discharge data set.Most importantly, we found that the increase in statistical performance matters, because models with better statistical performance produce substantially different results about which hospitals have better or worse than expected death rates.The figures do not directly address agreement.Rather, they illustrate the dispersion and correlation between fixed effects model standardized mortality rates, odds ratios, and random effects model standard mortality rates.To address model agreement, we presented tables that compare hospitals identified as significantly better (or worse) than expected and calculated the proportion of observed to expected agreement using the statistic. 3The models we compared demonstrated moderate agreement overall about which hospitals were better (or worse) than expected for each of the 3 indices.
P2-01-23: Seprase Promotes the Growth and Impairs the Migratory Ability of Breast Cancer Cells.
Authors: J Jia, TA Martin, WG Jiang
Journal: Cancer Research (2011)

Abstract Background: Seprase or Fibroblast Activation Protein alpha (FAP-a) is an integral membrane serine peptidase. It has been shown that it plays an important role in tumour proliferation, migration, invasion and angiogenesis. However, previous work has not satisfactorily explained both the suppression and promotion effects that have been observed. Furthermore, the interaction of Seprase with other membrane molecules or pathway had not been well investigated. This study aimed to investigate the role of Seprase in human breast cancer. Methods: The full length of Seprase cDNA was isolated from normal human prostate tissue using RT-PCR and then cloned into an expression vector (pEF6-V5 His, TOPO). Following confirmation of successful cloning, the plasmid was transfected into the to human breast cancer cell lines, MCF-7 and MDA-MB-231. The function of Separase in these two cell lines was then analysed using cell function assays and ECIS, and the potential interaction with other signalling pathways explored. Results: Compared with the MCF-7 wild type cells (MCF-7wt) and the MCF-7 cells transfected with pEF6/V5 empty vector (MCF-7pef), the MCF7 cells transfected with Seprase (MCF-7exp) had increased growth ability and impaired migratory ability. The growth rate of MCF-7exp cells was 1132.72% on day 5 while those of MCF-7wt and MCF-7pef control cells were 897.24% and 990.99% respectively (p=0.011 and 0.032). The resistance increase of MCF-7exp cells at 2 hours after wounding in ECIS assays was 478.22ohms compare with 1063.75 ohms and 1563.09 ohms in MCF-7wt and MCF-7pef control cells (p&amp;lt;0.05). In MDA-MB-231 cells, over-expression of Seprase resulted in impaired motility. The resistance increase of the MDA-MB-231 wild type cells (MDA-MB-231wt), MDA-MB-231 cells tranfected with pEF6/V5 vector (MDA-MB-231pef), and the MDA-MB-231 cells transfected with Seprase (MDA-MB-231exp) at 3 hours after wounding in ECIS assay were 216.75ohms, 216.00ohms and 120.16ohms respectively. The growth of MDA-MB-231 cells and the adhesion and invasion ability of both MCF-7 cells and MDA-MB-231 cells were not dramatically influenced with Seprase expression. An inhibitor to focal adhesion kinase (FAK) restored the reduced motility ability of both MCF-7exp cells and MDA-MB-231 exp cells. However, inhibitors to PI3K, ERK and ROCK had no influence on it. Conclusion: These results suggest that Seprase promotes proliferation but inhibits the migration of breast cancer cells by potentially regulating the FAK pathway. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-23.
INTRAVENOUS INJECTION OF NORMAL SALINE SOLUTION IN A SEVERE CASE OF HAEMATEMESIS: RECOVERY
Authors: H. E. Bruce-Porter
Journal: BMJ (1902)

To all surgeons who have frequently to operate upon patients in a condition of great exhaustion, to whom subsequently it is necessary'for a time to deny food in any considerable amount, some means of supplying their , systems with materials which shall in some measure, at all, events, make up to them for their hourly tissue waste must have often suggested itself as a serious desideratum.To some extent this waste may be replaced by rectal injeetions of fluid and peptonized foods.But this is a slow and imperfect method and only too frequently leads to irritability of the bowel, with rejection of the foods employed.For many years some of us have sought help in these cases from copious subcutaneous injections of normal saline solu- tions, and have had the best results from the practice in most cases.But I now desire briefly to draw attention to a method of introducing compounds into the circulation which may be looked upon in the light of foods, and not merely an innocuous addition to the blood of the water which is so rapidly lost by the lungs, skin, and kidneys, and sometimes by the intestine or by vomiting.This is the addition to our normal saline solutions of pure glucose.I learnt this from Professor K. Lennander, of Upsala, when he was my guest the year before last on the oocasion of his receiving the Hon.F.R.C.
Risk of thrombosis in patients with malignancy and heparin‐induced thrombocytopenia
Authors: Lucie Opatrny, Margaret N. Warner
Journal: American Journal of Hematology (2004)

Abstract Heparin‐induced thrombocytopenia (HIT) is a common immunological drug reaction. After exposure to heparin, some patients develop heparin dependent antibodies with no evidence of thrombosis, while others are at risk of thrombocytopenia, thrombosis, limb loss, and death. We conducted a retrospective chart review on all patients serologically positive for HIT by HPIA ELISA in a single tertiary‐care hospital, to determine whether patients with malignancy had an increased risk of thrombotic complications. Medical records of 55 patients who tested positive for HIT and met clinical criteria for HIT were analyzed. All patients had been treated with unfractionated heparin. Malignancy was diagnosed in 11 patients, either at surgery or post‐mortem examination. A higher rate of venous thrombosis and pulmonary embolism was observed in patients with HIT and malignant disease when compared to patients with no underlying malignancy (odds ratio 13.6, 95% CI 2.9–63.8). Am. J. Hematol. 76:240–244, 2004. © 2004 Wiley‐Liss, Inc.
Cell recovery during segmental intestinal perfusion in healthy subjects and patients with Crohn's disease.
Authors: O Ahrenstedt, F Knutson, L Knutson, M Krog, O Sjoberg, R Hallgren
Journal: Gut (1991)

BACKGROUND/AIM: The aim of this study was to investigate epithelial cell turnover in childhood enteropathy to establish whether common disease related mechanisms operate. Levels of epithelial cell proliferation were measured in children with food intolerance (cows9 milk protein intolerance and coeliac disease), and after infection with Giardia lamblia, Cryptosporidium, and enteropathogenic Escherichia coli. METHODS: Comparative measures of epithelial cell proliferation were performed by recording mitotic activity and MIB-1 immunoreactivity in proximal small intestinal biopsy specimens. RESULTS/CONCLUSIONS: A hyperplastic crypt response was evident in all of the disease states examined and was particularly pronounced in coeliac disease and in infection with enteropathogenic E coli, where mitotic and MIB-1 labelling indices were significantly raised above control values. In contrast with coeliac disease, increased crypt cell production rates in enteropathogenic E coli infection were also due to an expansion of the crypt proliferation compartment, without a comparable increase in crypt cell numbers. Crypt hyperplasia is therefore a common tissue response to mucosal damage in food allergy and infection, although disease specific mechanisms are evident.
90 CYCLOSPORINE AND TACROLIMUS HAVE DIFFERENT INHIBITORY EFFECTS ON TOLL-LIKE RECEPTOR SIGNALLING IN HEPATITIS C RECURRENCE POST LIVER TRANSPLANTATION
Authors: H. Howell, R. Sawhney, N. Skinner, D. Ratnam, P. Angus, P. Gow, K. Visvanathan
Journal: Journal of Hepatology (2012)
Osler as a Real Person
Authors: GEORGE T. HARRELL
Journal: Annals of Internal Medicine (1974)

Editorial Notes1 November 1974Osler as a Real PersonGEORGE T. HARRELL, M.D., F.A.C.P.GEORGE T. HARRELL, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-81-5-697 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWilliam Osler has been idolized in the writings of former students. This impression of a man too good to be true, without fault, always charitable, who never gossiped or spoke ill of anyone has been perpetuated by authors who never knew him firsthand. A paper in this issue by a distinguished scholar in medical history examines a "rough edge" and brings the famous physician into better perspective as a real person with human frailties (1).Roland cites instances of harsh words directed at students, practicing physicians, authors, pharmaceutical manufacturers, and public figures. Osler apparently felt it was good...References1. ROLAND C: Osler's rough edge. Ann Intern Med 81:690-692, 1974 LinkGoogle Scholar2. HARRELL G: Osler's practice. Bull Hist Med 47:545-568, 1973 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 2010 Eastridge Road, Timonium, Maryland PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySir William Osler (1849–1919) and the paternity of William Willoughby Francis (1878–1959): Review of the evidence 1 November 1974Volume 81, Issue 5Page: 697-698KeywordsFrailty ePublished: 1 December 2008 Issue Published: 1 November 1974 PDF downloadLoading ...
Antisense Targeting Protein Kinase C α and β1 Inhibits Gastric Carcinogenesis
Authors: Xiao-Hua Jiang, Shui-Ping Tu, Jian-Tao Cui, Marie C. M. Lin, Harry H. X. Xia, Wai Man Wong, Annie On-On Chan, Man Fung Yuen, Shi-Hu Jiang, Shiu-Kum Lam, Hsiang-Fu Kung, Jae Won Soh, I. Bernard Weinstein, Benjamin Chun-Yu Wong
Journal: Cancer Research (2004)

Abstract Protein kinase C (PKC) family, which functions through serine/threonine kinase activity, is involved in signal transduction pathways necessary for cell proliferation, differentiation, and apoptosis. Its critical role in neoplastic transformation and tumor invasion renders PKC a potential target for anticancer therapy. In this study, we investigated the effect of targeting individual PKCs on gastric carcinogenesis. We established gastric cancer cell lines stably expressing antisense PKCα, PKCβ1, and PKCβ2 cDNA. These stable transfectants were characterized by cell morphology, cell growth, apoptosis, and tumorigenicity in vitro and in vivo. PKCα-AS and PKCβ1-AS transfectants showed a different morphology with flattened, long processes and decreased nuclear:cytoplasmic ratio compared with the control cells. Cell growth was markedly inhibited in PKCα-AS and PKCβ1-AS transfectants. PKCα-AS and PKCβ1-AS cells were more responsive to mitomycin C- or 5-fluorouracil-induced apoptosis. However, antisense targeting of PKCβ2 did not have any significant effect on cell morphology, cell growth, or apoptosis. Furthermore, antisense inhibition of PKCα and PKCβ1 markedly suppressed colony-forming efficiency in soft agar and in nude mice xenografts. Inhibition of PKCα or PKCβ1 significantly suppressed transcriptional and DNA binding activity of activator protein in gastric cancer cells, suggesting that PKCα or PKCβ1 exerts their effects on cell growth through regulation of activator protein activity. These data provide evidence that targeting PKCα and PKCβ1 by antisense method is a promising therapy for gastric cancer.
Abstract 1479: IKK-epsilon contributes to the malignant progression of ovarian cancer
Authors: Christina M. Annunziata, Sarah Hsu, Lidia Hernandez, Elise Kohn, Ben Davidson
Journal: Cancer Research (2011)

Abstract Background and significance: The mechanism through which the NF-κB pathway affects the initiation, propagation and dissemination of ovarian cancer is unknown. I-κB kinases (IKKs) are key regulators of NF-κB signaling. Three IKK isoforms – α, β and ∈ – have been linked to oncogenesis, yet the precise components of NF-κB signaling mechanisms in ovarian cancer have not yet been dissected. IKK∈ was identified as an oncogene in breast cancer and has been associated with poor clinical outcome in ovarian cancer. This IKK isoform can regulate the innate immune response via activation of interferon-response factors, or can signal through classical NF-κB mechanisms by inactivating CYLD, a negative regulator of the pathway. Therefore, the molecular context is key to determining which oncogenic pathway is activated and how the signals will ultimately affect the cancer cel We hypothesized that IKK∈ drives ovarian cancer growth and metastasis. Methods: The expression of IKKe was determined in primary ovarian cancer specimens and human ovarian cancer cell lines. Ovarian cancer cell lines were depleted of IKKe using RNA interference and tested in functional assays, including anchorage-independent growth, basement membrane invasion, and heterotypic cell adhesion. Orthotopic xenograft mouse models were used to determine the role of IKKe in metastasis in vivo. Gene expression microarrays established an IKKe-specific signature in ovarian cancer. Results: We surveyed 120 ovarian cancer specimens (42 primary carcinomas, 78 solid metastases) for IKK∈ expression. Notably, cytoplasmic expression was elevated in metastatic lesions relative to primary tumor sites (p=0.03). RNA interference targeting IKK∈ in a panel of 5 metastatic ovarian cancer cell lines inhibited cell growth and prevented colony formation in soft agar. An ovarian cancer-specific IKK∈-regulated gene expression signature was identified using stably expressed shRNA targeting IKK∈. Pathway analysis of the signature indicated that IKK∈ regulates the expression of genes essential to diverse processes known to contribute to the malignancy of ovarian cancer, including TGFb and HIF1a pathways. Orthotopic xenograft experiments in mice demonstrated decreased aggressiveness of IKK∈-depleted ovarian cancer cells. Conclusion: These data provide evidence that IKK∈ plays a key role in ovarian cancer metastasis. Understanding IKK∈-regulated signaling in ovarian cancer will identify novel pathway interactions for context-specific therapeutics in the poor prognostic group of women whose ovarian cancers over-express IKK∈. 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 1479. doi:10.1158/1538-7445.AM2011-1479
X-Ray Mammography — Background to a Decision
Authors: Daniel S. Greenberg
Journal: New England Journal of Medicine (1976)

On August 23, the National Cancer Institute and the American Cancer Society terminated the routine use of x-ray mammography for women under age 50 who are enrolled in a five-year joint NCI-ACS nationwide project aimed at early detection of breast cancer. The decision, announced in "interim guidelines" sent to the directors of 27 centers that have been screening a total of 270,000 asymptomatic women 35 and over, was reached after frantic deliberations that even extended to an extraordinary poll of women employees. . .
Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice
Authors: Jian Liu, Adeline Divoux, Jiusong Sun, Jie Zhang, Karine Clément, Jonathan N Glickman, Galina K Sukhova, Paul J Wolters, Juan Du, Cem Z Gorgun, Alessandro Doria, Peter Libby, Richard S Blumberg, Barbara B Kahn, Gökhan S Hotamisligil, Guo-Ping Shi
Journal: Nature Medicine (2009)
Human Immunodeficiency Virus Antibody Testing
Authors: Keith Henry, Karen Willenbring, Kent Crossley
Journal: JAMA (1988)

A questionnaire that asked about policies concerning the use of human immunodeficiency virus (HIV) antibody tests was sent in January 1987 to the 200 hospitals in the United States that conduct infectious disease (ID) fellowship training (US ID hospitals) and to all 171 short-term—care Minnesota hospitals. Information was received from 189 of the US ID hospitals (94.5%) and from 160 (94%) of the Minnesota hospitals. Only 49% of the US ID hospitals and 37% of the Minnesota hospitals had an HIV antibody test—ordering policy; 47% of the US ID hospitals and 39% of the Minnesota hospitals had a specific educational program for physicians about the HIV antibody test; and 62% of the US ID hospitals and 41% of the Minnesota hospitals had an HIV autopsy policy. Marked variety existed in approaches to handling test results, obtaining patient consent, and providing risk-reduction information among the hospitals surveyed. These data suggest the need for a consensus on optimal use of HIV antibody testing at hospitals. (<i>JAMA</i>1988;259:1819-1822)
Effect of perfusate pH on the influx of 5-5′-dimethyl-oxazolidine-2,4-dione and dissociation of epidermal growth factor from the cell-surface receptor: the existence of the proton diffusion barrier in the Disse space
Authors: Makoto Ichikawa, Yukio Kato, Seiji Miyauchi, Yasufumi Sawada, Tatsuji Iga, Tohru Fuwa, Manabu Hanano, Yuichi Sugiyama
Journal: Journal of Hepatology (1994)