tbuckley/cabot-search huggingface dataset:
Genetic instability in different subclasses of breast cancer
Authors: Sharon B. Chang, Xin Lu, Ruth Gomes, Andrea Richardson, James D. Iglehart, Zhigang C. Wang
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

4437 

Background: Genetic instability, manifested by mutation, chromosomal amplification and chromosomal deletion, contributes to the progression and heterogeneity of breast cancer. In our previous study, we used gene expression profiling to cluster breast tumors into distinct subclasses defined as follows: IA, dominated by HER2-overexpressing tumors; IB, “basal-like” ER-and HER2-negative tumors; IIA, predominantly lower-grade ER-positive tumors (ductal and lobular); and IIB, dominated by higher-grade ER-positive tumors. These subclasses also have distinct patterns of allelic loss. Notably, IB tumors, characterized by high genetic instability, have a greater fractional loss of heterozygosity (FLOH) than the others. In the present study, we examined aneuploidy, another index of genetic instability, in these tumors. Methods: Two groups of human breast cancer samples were analyzed. DNA from an initial group of 40 formalin-fixed, paraffin-embedded tumor samples representing the four major subclasses of breast tumors and matched normal samples was allelotyped by Affymetrix HuSNP 1.5K array analysis. DNA content was determined by nuclear staining and quantitative image analysis. DNA from a second group of 19 frozen samples, consisting of IB tumors and a high-grade HER2-positive subset of IA tumors with matched normal samples, was allelotyped by the GeneChip SNP 10K array. Analysis of LOH and DNA copy number was done with dChipSNP software. Statistical analysis using ANOVA was performed. Results: IB tumors had a significantly higher frequency of fractional LOH than other tumors (34.4% in IB vs. 15% in IA, 6.7% in IIA, and 14.3% in IIB, p=0.0013). However, DNA content of the IB tumors was similar to the IA tumors (1.6 index units vs. 1.58, p=0.87). Comparison of IB tumors to a high-grade, HER2-positive subset of IA tumors revealed the latter had a slightly higher mean DNA content index than the IB (1.95 vs 1.6, p=0.08) but a significantly lower mean FLOH (18.1% vs. 34.4%, p=0.0053). Validation of these findings using a separate set of IB and high-grade HER2-positive IA tumors revealed similar trends. The IB tumors had a significantly higher mean FLOH than the high-grade HER2-positive subset of IA tumors (34.6% vs. 13.3%, p=0.025), whereas the mean DNA content index was significantly less (1.15 vs. 1.24, p = 0.01). Conclusions: Basal-like tumors have a high degree of FLOH but a low degree of aneuploidy, whereas the high-grade, HER2-positive tumors have a low degree of FLOH but a high degree of aneuploidy. Thus, the degree of FLOH correlates poorly with the DNA content, and neither FLOH nor measurements of DNA content alone are sufficient for accurate evaluation of genetic instability. The discrepancy between the degree of FLOH and the degree of aneuploidy in these two subclasses suggests that at least two distinct mechanisms may lead to genetic instability in breast cancer.
Abstract 20337: Implications of Invasively Measured Coronary Flow Reserve on Infarct Size Directly Following Reperfusion After Acute Myocardial Infarction in Both Humans and an Experimental Pig Model
Authors: Guus de Waard, Paul F Teunissen, Maurits R Hollander, Matthijs F Jansen, Lourens Robbers, Paul Knaapen, Niels van Royen
Journal: Circulation (2014)

Introduction:  An impaired coronary flow reserve (CFR) directly after primary PCI for treatment of acute myocardial infarction (AMI), is related to a worse clinical outcome. The prognostic relevance of CFR for early and late functional outcome and furthermore, the individual contribution of both the baseline and hyperemic component to CFR were investigated in this study.   Methods:  Intracoronary Doppler flow velocity measurements were obtained both before and directly after 90 minute balloon occlusion, with subsequent reperfusion, of the circumflex artery in an AMI pig model (n=11) and also directly after successful PCI in humans (n=34). Stable patients free from angiographic coronary artery disease served as a control group (n=134). CFR was defined as the ratio between hyperemic and basal average peak velocity (h-APV and b-APV). We correlated CFR to histological infarct size as percentage of left ventricle (IS%LV) in pigs at 7 days, and to 7 day and 3 month IS%LV as defined by cardiac magnetic resonance imaging in humans.   Results:  CFR was significantly correlated to IS%LV in both pigs (r = -0.61; p=0.048) and humans (r = -0.44; p   Conclusions:  A decrease in CFR is related to a larger infarct size and is observed in both patients as well as in healthy pig model of reperfused AMI, suggesting that pre-existing microvascular dysfunction does not explain the decreased CFR.
Weekly Temsirolimus and Bortezomib For Relapsed Or Refractory B-Cell Non-Hodgkin Lymphoma: A Wisconsin Oncology Network Phase II Study
Authors: Timothy S. Fenske, KyungMann Kim, Chong Zhang, John P. Farnen, Adedayo A. Onitilo, Jules H. Blank, Harish Ahuja, Tim Wassenaar, Rubina Qamar, Patrick Mansky, Anne Traynor, Ryan J. Mattison, Brad S. Kahl
Journal: Blood (2013)
Abstract 10623: Phosphorylation of Forkhead Transcription Factors Regulate Thrombin-Induced Proliferation of Human Vascular Smooth Muscle Cells
Authors: Shailaja Mahajan, Thomas Hohlfeld, Jens W Fischer, Karsten Schror, Bernhard H Rauch
Journal: Circulation (2011)

Forkhead box-O (FoxO) transcription factors regulate cellular processes including mitogenesis and cell cycle arrest. Phosphorylation of FoxO controls these cellular responses via the PI3K/AKT kinase pathway. Thrombin activates mitogenic signaling in vascular smooth muscle cells (VSMCs) via stimulation of the G-protein-coupled protease activated receptors (PAR-1, -3, and -4). Thereby thrombin elicits cellular responses that contribute to the pathogenesis of vascular disorders such as atherosclerosis. We investigated that FoxO proteins are downstream effectors of thrombin signaling in human VSMCs in vitro. Consequently, we aimed to determine whether phosphorylation of FoxO proteins upon stimulation of PARs is involved in thrombin-mediated proliferative responses in human VSMCs. The VSMCs were stimulated by thrombin (3U/ml) or PAR-1, -3 and -4-selective peptides. Protein expression was determined by immunoblotting; gene silencing was carried out using specific FoxO siRNAs. Mitogenesis and proliferation were ...
SUPERIOR AND INFERIOR VENAE CAVAE THROMBOSIS WITH POLYCYTHEMIA; REPORT OF A CASE
Authors: Oscar B. Ragins, George C. Coe
Journal: Annals of Internal Medicine (1943)

Case Reports1 September 1943SUPERIOR AND INFERIOR VENAE CAVAE THROMBOSIS WITH POLYCYTHEMIA; REPORT OF A CASEOSCAR B. RAGINS, M.D., GEORGE C. COE, M.D.OSCAR B. RAGINS, M.D.Search for more papers by this author, GEORGE C. COE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-19-3-496 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThrombosis of the superior vena cava is an unusual condition, but thrombosis of both the superior and inferior venae cavae is indeed rare. In an exhaustive review of the literature in 1936 Ochsner and Dixon1 collected 120 cases of superior vena cava thrombosis and added two of their own. Subsequently, individual cases have been reported by Szour and Berman,2 Blasingame,3 Buzzard,4 and Rutledge and Gray.5 In none of these, however, is any reference made to both superior and inferior venae cavae thrombosis.We wish to report such a case, diagnosed antemortem and proved at autopsy, with several unusual findings not...Bibliography1. OCHSNERDIXON ALJ: Superior vena caval thrombosis; review of literature and report of cases of traumatic and infectious origin, Jr. Thorac. Surg., 1936, v, 641-672. CrossrefGoogle Scholar2. SZOURBERMAN MR: Thrombosis of superior vena cava in pulmonary tuberculosis; case, Rev. de la tuberc., 1936, ii, 1068-1075. Google Scholar3. BLASINGAME FJ: Occlusion of the superior vena cava and its tributaries, associated with established collateral circulation, Arch. Path., 1938, xxv, 361-364. Google Scholar4. BUZZARD EM: Thrombosis of superior vena cava, Brit. Jr. Tuberc., 1940, xxxiv, 39-44. CrossrefGoogle Scholar5. RUTLEDGEGRAY DIHK: Indeterminate type of obstruction of the superior vena cava, Proc. Staff Meet. Mayo Clin., 1939, xiv, 337-340. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Chicago, Illinois*Received for publication November 17, 1941. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byRetroperitoneal Venous DiseasesRetroperitoneal Venous DiseasesInferior Vena Cava Obstruction Clinical Manifestations, Diagnostic Methods, and Related ProblemsMORRIS E. MISSAL, M.D., F.A.C.P., JAMES A. ROBINSON, M.D., RONALD W. TATUM, M.D.The nephrotic syndrome following thrombosis of the inferior vena cavaObstructions of the superior vena cava 1 September 1943Volume 19, Issue 3Page: 496-501KeywordsAutopsyPolycythemiaThrombosis ePublished: 1 December 2008 Issue Published: 1 September 1943 PDF downloadLoading ...
Plasmochin As An Aid in Malaria Prevention
Authors: Neil P. Mcphail
Journal: Annals of Internal Medicine (1931)

Article1 March 1931Plasmochin As An Aid in Malaria PreventionNEIL P. MCPHAIL, M.D.NEIL P. MCPHAIL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-4-9-1217 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDuring the twenty-two years in which the Medical Department of the United Fruit Company has made earnest efforts to reduce the incidence of malaria in the Motagua Valley where they operate, dependence was placed for the first number of years on two main measures.On one hand all collections of water in close proximity to campus were drained when possible, and treated with oil or Paris Green when drainage was impractical. These measures were directed against the breeding of the Anopheles mosquito. On the other hand the human carrier was treated with lengthy courses of quinine, arsenic, and other tonic... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Puerto Barrios, Guatemala*From the Quirigua Hospital, Puerto Barrios, Guatemala. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1931Volume 4, Issue 9Page: 1217-1220KeywordsArsenicMalariaOilsQuinine ePublished: 1 December 2008 Issue Published: 1 March 1931 PDF downloadLoading ...
Abstract 10258: Left Ventricular Dyssynchrony of Contraction and Reduced Compliance Predict Short-Term Clinical Worsening in Transplant Candidates with Dilated Cardiomyopathy
Authors: Michael Dandel, Hans B Lehmkuhl, Christoph Knosalla, Roland Hetzer
Journal: Circulation (2010)

Objective: With increasing heart transplant (HTx) waiting times, anticipation of short-term cardiac worsening, and finding predictors of short-term outcome without HTx or ventricular assist device ...
Abstract 299: Taurine Is Essential For Cellular Osmoregulation In The Heart
Authors: Takashi Ito, Yasushi Kimura, Mika Takai
Journal: Circulation (2007)

[Background] Taurine, a sulfur-containing β-amino acid, is the most abundant free amino acid in mammalian tissues, especially cardiac muscles. Taurine is reported to be beneficial for patients with congestive heart failure; however, it remains to be fully elucidated how taurine exhibits its cardioprotective effects. To address the molecular mechanisms for its cardioprotective roles, we investigated functional and morphological phenotypes in mice lacking taurine transporter gene (TauTKO). [Methods and Results] Taurine content was dramatically decreased in hearts of TauTKO mice. Echocardiographic analysis revealed that TauTKO hearts showed impaired cardiac output (Fractional shortening (%): 32.3 ± 3.6 (wild) vs 22.5 ± 2.2 (TauTKO), p &lt;0.05). Histological analyses showed ventricular wall thickness was thinner in TauTKO mice than wild-type littermates, which was concomitant with decreased myocyte sizes in TauTKO ventricles (211.2 ± 5.0 v.s. 153.6 ± 5.2 μm 2 , p &lt;0.01). Furthermore, to analyze the changes in gene expressions in TauTKO hearts, we performed microarray analyses using total RNA from hearts muscles. Importantly, hypertonicity-inducible genes, such as hspa1a/b (heat shock protein 70), slc38a2 (amino acid transporter-2) and s100a4 (S100 calcium binding protein A4), were upregulated more than 1.7-fold in cardiac muscles of TauTKO mice, compared with control. The inductions of these genes were verified by real time quantitative RT-PCR (hspa1a/b; 4.8 ± 1.3 (fold), slc38a2; 3.3 ± 0.5, s100a4; 1.7 ± 0.13), suggesting that hypertonicity-inducible signaling pathways are activated in TauTKO hearts. Interestingly, the upregulation of these hypertonicity-inducible genes was also observed in skeletal muscles that exhibited decreased cell size in TauTKO mice, proposing the possibility that taurine-mediated osmoregulatory signals are widely utilized in various kinds of cell lineages as a novel cytoprotective system. [Conclusion] Intracellular taurine depletion leads to cellular osmotic impairment and results in cardiac dysfunction, accompanied by myocyte size decrease. Taurine transporter could be essential for the maintenance of intracellular osmotic homeostasis in cardiac myocytes.
Functional interaction between Mrp4 (abcc4) and Bcrp (abcg2) as revealed by the single and double-knockout mouse
Authors: Kazumasa Takenaka, Jessica Morgan, Masashi Adachi, Daxi Sun, Clinton Stewart, Markos Leggas, Karin F Ejendal, Christine A Hrycyna, John D Schuetz
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

606 

Recent studies from our laboratory and others (Mol. Cancer Therap. 4, 547, 2005) have demonstrated that Mrp4 can transport and confer resistance to camptothecins. It is well known that Bcrp also transports and confers resistance to camptothecins. Bcrp is prominently expressed at the apical surface of polarized cells (intestinal epithelium), whereas Mrp4 is expressed, depending upon the tissue, at either the apical or basolateral membrane in vivo (MCB. 24, 7612 2005). Thus, it is possible in some tissues that Mrp4 and Bcrp might functionally oppose each other in vivo. Moreover, we have noted that in the absence of Mrp4 some tissues upregulated Bcrp, further suggesting these proteins have a functional overlap and might compensate for one another. To understand the role of these transporters in vivo we have developed the Mrp4 and Bcrp double-knockout (DKO) mice and performed various analyses. The mice are viable and fertile and gain weight as expected. Hematologic analysis reveals no disruption in formation of mature myeloid or lymphoid elements. Given the lack of obvious physiological impairment in the DKO, we will report on how the absence of each transporter and both together affects chemotherapeutic drug distribution in vivo. These findings will reveal the contribution of each transporter to their common substrates.
Imported case of MERS-CoV infection identified in China, May 2015: detection and lesson learned
Authors: J Wu, L Yi, L Zou, H Zhong, L Liang, T Song, Y Song, J Su, C Ke
Journal: Eurosurveillance (2015)

At the end of May 2015, an imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was confirmed in China. The patient is in a stable condition and is still undergoing treatment. In this report, we summarise the preliminary findings for this imported case and the results of contact tracing. We identified 78 close contacts and after 14 days of monitoring and isolation, none of the contacts presented symptoms and all tested negative for MERS-CoV.
Abstract 16355: Prognostic Significance of QRS Fragmentation in the MADIT-CRT
Authors: Grzegorz Pietrasik, Andrew Brenyo, Scott McNitt, Luigi Padeletti, Arthur Moss, Wojciech Zareba
Journal: Circulation (2010)

Background: Fragmentation of QRS complex (fQRS) was proposed as an ECG marker of increased mortality in patients with LV systolic dysfunction. The aim of this study was to evaluate the prognostic s...
Abstract 5675: Brugada-Type ST Segment Elevation after Sodium Channel Blockade is Caused by Right Ventricular Excitation Failure in Discontinuous Myocardium
Authors: Mark G Hoogendijk, Mark Potse, Andre C Linnenbank, Arie O Verkerk, Hester M den Ruijter, Eva C Klaver, Shirley C van Amersfoorth, Leander Beekman, Connie R Bezzina, Arthur A Wilde, Ruben Coronel
Journal: Circulation (2008)

Introduction: Brugada-type ST segment elevation has been associated with reduced sodium channel function and structural heart disease and is a risk marker for sudden cardiac death. Depolarizing and repolarizing abnormalities in the right ventricular wall have been described in patients. The mechanism of ST segment elevation however, is still debated. We determined depolarization and repolarization characteristics in an isolated heart of a young patient carrying a sodium channel mutation previously described in a family with Brugada syndrome. Methods and Results: A 15-year old female patient with a loss-of-function mutation (G752R) in the gene encoding the cardiac sodium channel underwent cardiac transplantation for end-stage heart failure in dilated cardiomyopathy. The explanted, perfused heart was submerged in perfusion fluid. We simultaneously recorded an “Einthoven” configuration pseudo-ECG and 194 unipolar electrograms from the endo- and epicardium of both ventricles. At baseline, a single shortly coupled premature stimulus resulted in more fractionated electrograms in the right than left ventricle (38 vs 6%, p &lt; 0.001, Z-test). After sodium channel blockade by ajmaline, ST segment elevation of 0.3 mV was observed in pseudo-aVR which coincided with the virtual disappearance of the QRS complex in unipolar electrograms at the basal epicardium of the right ventricle followed by monophasic ST segment elevation. The local origin of this phenomenon was demonstrated by Laplacian electrograms. Neither early repolarization nor late activation correlated with the ST-change. Marked epicardial fatty infiltration was present at sites of local ST segment elevation, but not elsewhere. Simulations in a bidomain whole-heart computer model showed that either sodium current reduction or random replacement of 50% of the right ventricular epicardium by fat alone does not cause ST segment elevation. In combination however, part of the epicardial myocardium was not excited throughout the cardiac cycle by current-to-load mismatch resulting in Brugada-type ST segment elevation. Conclusions: Brugada-type ST segment elevation after sodium channel blockade is caused by excitation failure in discontinuous myocardium at the right ventricular epicardium.
US Supreme Court throws out law that forced doctors in North Carolina to deliver antiabortion message
Authors: O. Dyer
Journal: BMJ (2015)

A North Carolina law that forced abortion doctors to seek informed consent while providing a mandatory ultrasound and reading a state sanctioned antiabortion message will be struck from the books after the US Supreme Court refused to hear an appeal from the state.

That refusal makes final the December decision of the US Court of Appeals for the Fourth Circuit, which ruled the law unconstitutional on the grounds that it violated the doctor’s first amendment right to free speech. “The state cannot commandeer the doctor-patient relationship to compel a physician to express its preference to …
Essential elements of the treatment must be identified
Authors: S. M Lawrie, A. J Pelosi
Journal: BMJ (1996)

EDITOR,—We have several practical and theoretical concerns about Michael Sharpe and colleagues' study of cognitive behaviour therapy in the chronic fatigue syndrome.1 The authors managed to obtain almost 100% uptake of treatment and compliance among patients who were attending an infectious diseases clinic and were strongly convinced that their chronic fatigue had a physical cause. We would struggle to engage our patients similarly, even with two hours for an initial appointment, and we could not offer …
Evaluation and Treatment of Patients With Lower Extremity Peripheral Artery Disease
Authors: Manesh R. Patel, Michael S. Conte, Donald E. Cutlip, Nabil Dib, Patrick Geraghty, William Gray, William R. Hiatt, Mami Ho, Koji Ikeda, Fumiaki Ikeno, Michael R. Jaff, W. Schuyler Jones, Masayuki Kawahara, Robert A. Lookstein, Roxana Mehran, Sanjay Misra, Lars Norgren, Jeffrey W. Olin, Thomas J. Povsic, Kenneth Rosenfield, John Rundback, Fadi Shamoun, James Tcheng, Thomas T. Tsai, Yuka Suzuki, Pascal Vranckx, Bret N. Wiechmann, Christopher J. White, Hiroyoshi Yokoi, Mitchell W. Krucoff
Journal: Journal of the American College of Cardiology (2015)
Abstract 21243: Evaluation of Heavily Calcified Vessels with Coronary CT Angiography: Comparison of Iterative and Filtered Back Projection Image Reconstruction Techniques
Authors: Matthias Renker, U J Schoepf, Markus Weininger, J M Kerl, Ralf W Bauer, Thomas Henzler, Thomas J Vogl
Journal: Circulation (2010)

Introduction: Heavy calcifications remain a limitation of coronary CT angiography (cCTA) and decrease the accuracy of this test for stenosis detection. Hypothesis We assessed the hypothesis that the novel iterative image reconstruction technique allows for more precise delineation of calcified plaques at cCTA in comparison to traditional filtered back projection (FBP). Methods: Dual source cCTA studies of 30 patients (18men; 57±11 years) with Agatston scores of >400 were included prospectively. Image reconstruction was performed with FBP and with iterative reconstruction in image space (IRIS) using corresponding vascular algorithms. Image noise was evaluated in a region of interest in the aortic root. To compare the two reconstruction techniques regarding calcified plaque delineation, the volume of heavy coronary artery calcifications was measured using a threshold based volumetry tool. Two experienced, blinded observers subjectively rated image quality on a 5-point scale and interpreted both, FBP and IRI...