tbuckley/cabot-search huggingface dataset:
β Fibrinogen Gene Polymorphisms Are Associated With Plasma Fibrinogen and Coronary Artery Disease in Patients With Myocardial Infarction
Authors: IsabelleBehague, OdettePoirier, VivianeNicaud, AlunEvans, DominiqueArveiler, GéraldLuc, Jean-PierreCambou, Pierre-YvesScarabin, LucienneBara, FionaGreen, FrançoisCambien
Journal: Circulation (1996)

Background Polymorphisms of the β fibrinogen gene have been shown to affect plasma fibrinogen levels and the risk of peripheral arterial disease. We now present the results of a detailed analysis of the β fibrinogen gene in relation to plasma fibrinogen and to the severity of coronary artery disease (CAD) in patients with myocardial infarction (MI) in the ECTIM Study. Methods and Results Ten polymorphisms of the β fibrinogen gene, including five new polymorphisms identified by single-strand conformation polymorphism analysis, and one polymorphism in the 3′ flanking region of the α fibrinogen gene were investigated in 565 patients with MI and 668 control subjects. The polymorphisms were in tight linkage disequilibrium and the genotype frequencies were similar in patients with MI and control subjects. In the multivariate analysis, only two polymorphisms, β Hae III (P<.0003) and β-854 (P<.01), were independently associated with plasma fibrinogen. The significant association between β fibrinogen polymorphisms...
Estradiol and Progestins Differentially Modulate Leukocyte Infiltration After Vascular Injury
Authors: DongqiXing, AndrewMiller, LeaNovak, RicardoRocha, Yiu-FaiChen, SuzanneOparil
Journal: Circulation (2004)

Background— Inflammation plays an important role in the response to endoluminal vascular injury. Estrogen (17β-estradiol, E2) inhibits neointima formation in animal models, and the progestin medroxyprogesterone acetate (MPA) blocks this effect. This study tested the hypothesis that E2 inhibits the migration of inflammatory cells, particularly granulocytes, into the rat carotid arteries after acute endoluminal injury and that MPA blocks this effect. Methods and Results— Ovariectomized rats were randomly divided into subgroups and treated with E2, MPA, E2+MPA, or vehicle and subjected to balloon injury of the right carotid artery. After 1, 3, or 7 days, rats were euthanized, and carotid arteries (injured and control) were analyzed for inflammatory cells by flow cytometry. At 1 day, granulocytes (HIS48+ and CD45+), monocyte/macrophages (Mar1+ and CD45+), and T lymphocytes (CD3+ and CD45+) were increased 26-fold, 12-fold, and 3-fold, respectively, in injured compared with contralateral control arteries of veh...
Oxidative stress induced by early cycles of combination chemotherapy in chemonaive and radionaive breast cancer patients.
Authors: Victor C. Kok, Wan-Seng Ko, C.H. Guo, P.C. Chen
Journal: Journal of Clinical Oncology (2012)

e11561 Background: Chemotherapy-induced oxidative stress (CIOS) can be altered multifactorially in time course of treatment. Initial changes of CIOS in the breast cancer patients are not clear. OBJECTIVES: IRB-approved prospective study of the changes of CIOS in chemo-naïve and radiotherapy-naïve breast cancer patients who undergo chemotherapy(CT) or radiotherapy(RT) in either adjuvant or metastatic settings. Methods: Exclusion criteria: Patient who has prior exposure to CT or RT, active infection, connective tissue disorder, been taking antioxidant agent(s), active hepatitis, liver cirrhosis, renal insufficiency and no written informed consent. Blood samplings were done before CT or RT and day 22 since chemotherapy or day 29 since RT. Serum analyzed for glutathione peroxidase(GSH-Px), glutathione reductase(GR), Vit.E, malondialdehyde (MDA), and trace elements including Zn, Cu, Fe, Se. Results: 10 patients and 10 healthy volunteers were entered. Median age: 47.5 (R: 38~80); Tumor type; infiltrating ductal ca: 8 pts; lobular ca: 1; mucinous: 1. Stage: IIA: 4 pts; IIB: 1; IIIA: 3; IIIB: 0; IIIC: 1; Relapsed: 1. ECOG 0/1: 9/1 pts; Regimens: FEC: 5 pts, CAF: 1, EC: 2, CMF: 1; RT: 1. After 1 cycle of CT or 28 days of RT: GSH-Px was significantly increased (P=0.0003); GR increased (P=0.0002); Vit. E increased (1-sided P=0.028); MDA decreased (P=0.0073) and Zn decreased (P=0.0162). Contrary to some oncologists initial expectations, the early changes after chemotherapy or radiotherapy are elevation of body's antioxidative capacity. Conclusions: Spontaneous counterbalance of CIOS after initial cycles of chemotherapy is suggested from this study.
Abstract 5462: Functional characterization of potential gain-of-function p53 mutants in esophageal squamous cell carcinoma
Authors: Valen Z. Yu, Maria L. Lung
Journal: Cancer Research (2018)

Abstract One of the most frequently mutated genes reported in human cancers is TP53. Esophageal squamous cell carcinoma (ESCC) has an extremely high frequency of p53 mutations of 60-90% in ESCC patients. Evidence of gain-of-function (GOF) p53 mutations that exert wild-type (WT) function-independent oncogenic effects are emerging. We aim to determine the functional role of several candidate GOF p53 mutations in ESCC and explore their clinical utility for prognostication and as potential treatment targets. In our recent study of Hong Kong ESCC specimens, we detected TP53 alterations in over 90% of ESCC tumors, ~36% of which are candidate GOF mutations verified in other cancers. By analyzing published ESCC sequencing data, we showed that patients from the high-risk ESCC region show frequent candidate GOF p53 mutants. We applied the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technique to functionally knockout (fKO) mutant p53 protein expression in various ESCC cell lines with different endogenous p53 mutants and subject them to in vivo and in vitro functional assays. Interestingly, only KYSE150 cells with an endogenous p53R248Q mutation show reduced tumor growth in nude mice after p53-fKO, suggesting that there is a specific mutant p53 that confers oncogenic features in ESCC. Consistently, only KYSE150 p53-fKO cells show reduced colony formation in three-dimension in vitro culture. Tyrosine phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3) is significantly reduced in KYSE150 p53-fKO cells, suggesting that regulation of the STAT3 pathway contributed to the oncogenic feature of the GOF p53 mutant. p53R248Q exhibits concentrated subcellular localization to the membrane fraction (including ER, mitochondria, etc.) and shows increased resistance to HSP90/HDAC inhibition-induced protein degradation, as compared to other p53 mutants. Together, these results suggest a GOF role of certain mutant p53 proteins with specific characteristics. Targeting such mutants and/or related oncogenic pathways may be of therapeutic benefit. Acknowledgement: We acknowledge the Research Grants Council of Hong Kong Special Administrative Region for General Research Fund support (17109515 to M.L.L). Citation Format: Valen Z. Yu, Maria L. Lung. Functional characterization of potential gain-of-function p53 mutants in esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5462.
Multiscale Motion Mapping
Authors: MichaelSühling, ChristianJansen, MuthuvelArigovindan, PeterBuser, StephanMarsch, MichaelUnser, PatrickHunziker
Journal: Circulation (2004)

Background— Objective, quantitative, segmental noninvasive/bedside measurement of cardiac motion is highly desirable in cardiovascular medicine, but current technology suffers from significant drawbacks, such as subjectivity of conventional echocardiographic reading, angle dependence of tissue Doppler measurements, radiation exposure by computer tomography, and infrastructure requirements in MRI. We hypothesized that computer vision technology could represent a powerful new paradigm for quantification in echocardiography. Methods and Results— We present multiscale motion mapping, a novel computer vision technology that is based on mathematical image processing and that exploits echocardiographic information in a fashion similar to the human visual system. It allows Doppler- and border-independent determination of motion and deformation in echocardiograms at arbitrary locations. Correctness of the measurements was documented in synthetic echocardiograms and phantom experiments. Exploratory case studies dem...
Cineangiocardiographic Studies of the Left Ventricle in Patients with Angina Pectoris
Authors: Larsbjörk, Ingemarcullhed, Adarhallén
Journal: Circulation (1967)

The findings at coronary angiography and left ventricular cineangiography were compared with clinical data in 52 cases of coronary artery disease. A semiquantitative estimation of left ventricular end-diastolic and end-systolic volumes was used, as well as the identification of local dysfunction in the left ventricular wall. The findings at ventriculography had no relation to the functional classification or the maximal physical work capacity. Thus the limiting factor is angina pectoris and not primarily changes in the left ventricular wall after infarction. Similarly, retrograde filling of stenosed arteries by collateral channels was not correlated to the degree of left ventricular dysfunction or to physical work capacity. Patients with slight to moderate coronary artery stenosis had a normal left ventricular contraction pattern, and in no instance did the electrocardiogram indicate previous myocardial infarction. On the other hand, a normal electrocardiogram as well as a normal left ventricular contract...
Optimizing Cancer Treatment Using Game Theory
Authors: Katerina Stanková, Joel S. Brown, William S. Dalton, Robert A. Gatenby
Journal: JAMA Oncology (2018)

While systemic therapy for disseminated cancer is often initially successful, malignant cells, using diverse adaptive strategies encoded in the human genome, almost invariably evolve resistance, leading to treatment failure. Thus, the Darwinian dynamics of resistance are formidable barriers to all forms of systemic cancer treatment but rarely integrated into clinical trial design or included within precision oncology initiatives.We investigate cancer treatment as a game theoretic contest between the physician's therapy and the cancer cells' resistance strategies. This game has 2 critical asymmetries: (1) Only the physician can play rationally. Cancer cells, like all evolving organisms, can only adapt to current conditions; they can neither anticipate nor evolve adaptations for treatments that the physician has not yet applied. (2) It has a distinctive leader-follower (or "Stackelberg") dynamics; the "leader" oncologist plays first and the "follower" cancer cells then respond and adapt to therapy. Current treatment protocols for metastatic cancer typically exploit neither asymmetry. By repeatedly administering the same drug(s) until disease progression, the physician "plays" a fixed strategy even as the opposing cancer cells continuously evolve successful adaptive responses. Furthermore, by changing treatment only when the tumor progresses, the physician cedes leadership to the cancer cells and treatment failure becomes nearly inevitable. Without fundamental changes in strategy, standard-of-care cancer therapy typically results in "Nash solutions" in which no unilateral change in treatment can favorably alter the outcome.Physicians can exploit the advantages inherent in the asymmetries of the cancer treatment game, and likely improve outcomes, by adopting more dynamic treatment protocols that integrate eco-evolutionary dynamics and modulate therapy accordingly. Implementing this approach will require new metrics of tumor response that incorporate both ecological (ie, size) and evolutionary (ie, molecular mechanisms of resistance and relative size of resistant population) changes.
Abstract 17262: Outcomes following High Risk Surgery provided as an Alternative to Transplant in patients with End-stage Heart Disease
Authors: HiroyukiKawajiri, LisaGarrard, CedricManlhiot, HeatherRoss, DiegoDelgado, FilioBillia, MichaelMcDonald, VivekRao
Journal: Circulation (2014)

Background: Heart transplant (Tx) and ventricular assist device (VAD) have become established treatments for end stage heart failure; however, both treatments still have unsolved problems. Patients referred for Tx or VAD are often found to have cardiac lesions amenable to surgical intervention. We examined the results of conventional surgery in patients with severe left ventricular dysfunction to explore the possibility of high risk surgery as an alternative option. Methods: We reviewed our institutional database and identified all surgical patients referred to our senior author with severe LV dysfunction (EF<20%). We then selected patients who were initially referred for consideration of Tx or VAD, but were instead offered conventional surgery. All patients underwent evaluation for Tx candidacy and thus were prospectively stratified into Tx eligible (Tx-E) or Tx non-eligible (Tx-NE) groups. We compared outcomes stratified by Tx eligibility as well as by type of surgery. Results: A total of 133 patients w...
Phosphatidylinositol 3-Kinase/Akt Regulates Angiotensin II–Induced Inhibition of Apoptosis in Microvascular Endothelial Cells by Governing Survivin Expression and Suppression of Caspase-3 Activity
Authors: HirokazuOhashi, HitoshiTakagi, HideyasuOh, KiyoshiSuzuma, IzumiSuzuma, NorikoMiyamoto, AkiyoshiUemura, DaisukeWatanabe, TomoakiMurakami, TakeshiSugaya, AkiyoshiFukamizu, YoshihitoHonda
Journal: Circulation Research (2004)

Angiotensin II (Ang II) plays essential roles in vascular homeostasis, neointimal formation, and postinfarct remodeling. Although Ang II has been shown to regulate apoptosis in cardiomyocytes and vascular smooth muscle cells, its role in vascular endothelial cells (ECs) remains elusive. To address this issue, we first performed TUNEL and caspase-3 activity assays with porcine microvascular ECs challenged by serum deprivation. Ang II significantly reduced the ratio of apoptotic cells and caspase-3 activity. The Ang II type 1 receptor (AT1) was responsible for these effects. Among the signaling molecules downstream of AT1, we revealed that PI3-kinase/Akt pathway plays a predominant role in the antiapoptotic effect of Ang II. Interestingly, the expression of survivin, a central molecule of cell survival, increased after Ang II stimulation. Overexpression of a dominant-negative form of Akt abolished both Ang II–induced antiapoptosis and survivin protein expression. In a murine model of hyperoxygen-induced ret...
Abstract 14: Midlife Cardiorespiratory Fitness is Associated with Lower Incidence of Depression and Cardiovascular Death with or without Incident Depression in Later Life
Authors: Benjamin L Willis, David S Leonard, Carolyn E Barlow, Shannon J Fitzgerald, Scott B Martin, Laura F DeFina
Journal: Circulation (2016)

Introduction: Depression disorders are common and debilitating conditions which can affect older individuals, especially those with cardiovascular disease (CVD). The association of midlife cardiorespiratory fitness (fitness), an objective measure of habitual physical activity, with later-life depression is not fully understood. Furthermore, although depression is associated with incident CVD, little is known about the long term association of midlife fitness with CVD death following the onset of depression decades later. Hypothesis: Fitness measured in midlife will be inversely associated with depression in later life and risk of CVD death with or without intercurrent depression. Methods: Linking participant data from the Cooper Center Longitudinal Study with Medicare claims files, we studied 16,728 participants (19% women, mean age 51) without prior history of depression or CVD, who received Medicare coverage from 1999-2009. Midlife fitness was estimated by Balke protocol treadmill time in metabolic equivalents and grouped into age and sex-specific categories: low, moderate, and high fitness. Other midlife risk factors were measured using standard protocols. Depression diagnosis was defined from Medicare claims files according to established algorithms and CVD mortality was determined from National Death Index records. Multivariate survival modeling was used to assess the associations between midlife fitness and time to any of three later life events: incident depression, CVD death without incident depression, and CVD death following incident depression. The model was adjusted for midlife age, gender, year of examination, smoking, systolic blood pressure, cholesterol, BMI, and fasting glucose. Results: After 109,143 person years of Medicare follow-up, we observed 2379 cases of incident depression, 570 CVD deaths without incident depression and 218 CVD deaths following incident depression. High fitness in midlife was associated with a 24% lower risk of depression (hazards ratio [HR] 0.76, 95% CI 0.67-0.86 compared to low fit). High fitness was also associated with a 63% lower risk of CVD death without incident depression (HR 0.37, 95% CI 0.30-0.47 compared to low fit) and 50% lower risk of CVD death (HR 0.50, 95% CI 0.34-0.72 compared to low fit) following incident depression. Conclusion: Midlife fitness, a modifiable CVD risk factor, is associated with lower risk of depression in later life, lower risk of CVD death without incident depression, and lower risk of CVD death following incident depression decades later. These findings suggest the importance of fitness in primary prevention of depression and mortality in older age.
Id1 Gene Transfer Confers Angiogenic Property on Fully Differentiated Endothelial Cells and Contributes to Therapeutic Angiogenesis
Authors: KoichiNishiyama, KentaroTakaji, KeiichiroKataoka, YukikoKurihara, MichihiroYoshimura, AtsushiKato, HisaoOgawa, HirokiKurihara
Journal: Circulation (2005)

Background— Transplantation of endothelial progenitor cells has been proposed as a potential strategy for therapeutic revascularization. However, the limited endogenous cell pool and the related technical difficulties constitute clinically important disadvantages to autologous transplantation. In this study we investigated whether fully differentiated endothelial cells (ECs) modified with gene transfer of Id1, a helix-loop-helix transcription factor involved in angiogenesis, have the potential to contribute to therapeutic angiogenesis. Methods and Results— The Id1 gene was transferred into human umbilical vein ECs (HUVECs) via a Sendai virus vector. Id1 stimulated migration, proliferation, and capillary-like tube/cord formation of HUVECs. In addition, Id1 reduced serum deprivation–induced HUVEC apoptosis, as shown by FACS analysis with annexin V and TUNEL staining. Transplantation of Id1-overexpressing HUVECs accelerated recovery of blood flow as evaluated by laser-Doppler perfusion imaging, increased cap...
Syndecan-4 Prevents Cardiac Rupture and Dysfunction After Myocardial Infarction
Authors: YutakaMatsui, MasahiroIkesue, KeikoDanzaki, JunkoMorimoto, MamiSato, ShinyaTanaka, TetsuhitoKojima, HiroyukiTsutsui, ToshimitsuUede
Journal: Circulation Research (2011)

Rationale:Syndecan-4 (Syn4), a cell-surface heparan sulfate proteoglycan, has been detected in the infarct region after myocardial infarction (MI), but its functional significance has not been elucidated. Objective:We examined whether and how Syn4 regulates the cardiac healing process after MI. Methods and Results:Although the heart in Syn4-deficient (Syn4−/−) mice was morphologically and functionally normal, Syn4−/− mice exhibited impaired heart function and increased mortality rate as a result of cardiac ruptures after MI. Cardiac ruptures in Syn4−/− mice were associated with reduced inflammatory reaction and impaired granulation tissue formation during the early phase of MI, as evidenced by reduced numbers of leukocytes, fibroblasts, myofibroblasts, macrophages, and capillary vessels, along with reduced extracellular matrix protein deposition in the infarct region after MI. Transforming growth factor-β1–dependent cell signaling was preserved, whereas cell migration, fibronectin-induced cell signaling, ...
Doctors share their tips for new starters
Authors: Abi Rimmer
Journal: BMJ (2018)

Junior doctors starting their working lives this week should keep nurses on their side, remember to take regular breaks, observe as much as they can, and, above all, try to enjoy themselves, colleagues have advised.

Gordon Morrison‏ (@GDIMorrison), an acute medicine consultant at University Hospital Southampton NHS Foundation Trust, tweeted four tips for new doctors: “1) Listen to the nurses. They are rarely wrong when they come to you worried about …
Abstract 9919: ST-Segment Elevation in Lead aVR is the Strongest Predictor of 30-Day Mortality in Patients With Type A Acute Aortic Dissection
Authors: MasamiKosuge, KeijiUchida, SusumuIsoda, ToshiakiEbina, KiyoshiHibi, MunetakaMasuda, SatoshiUmemura, KazuoKimura
Journal: Circulation (2015)

Introduction: We investigated the prognostic value of ST-segment elevation in lead aVR (ST↑aVR) at presentation ECG in type A acute aortic dissection (AAD). Hypothesis: In type A AAD, ischemic ST-T changes at presentation have been shown to be associated with poor outcomes. ST↑aVR, an ECG marker of severe acute myocardial ischemia, may provide important prognostic information. Methods: We studied the relation of ECG findings to clinical features on admission and 30-day mortality in 280 patients who were admitted within 6 h from symptom onset and underwent emergency surgery for type A AAD. Patients with bundle branch block or left ventricular hypertrophy were excluded. Patients were divided into the 3 groups according to admission ECG findings: no significant ST-T changes (n=96, G-A); the absence (n=142, G-B) or the presence (n=42, G-C) of ST↑aVR ≥0.5 mm with ST-T changes in other leads. Estimated glomerular filtration rate (eGFR) was measured on admission, and renal dysfunction was defined as an eGFR <60 ...
Abstract 12924: Expansion of Extracellular Space Assessed by Post-contrast T1 Value is Closely Related to Diastolic Dysfunction and Neurohormonal Activation in Patients with Dilated Cardiomyopathy
Authors: Ji Hyun Yoon, Jung Woo Son, Hye-Moon Chung, Jung-Joon Cha, Chul-Hwan Park, Young-Jin Kim, Hyuk-Jae Chang, Geu-Ru Hong, Tae Hoon Kim, Jong-Won Ha, Byoung Wook Choi, Se-Joong Rim, Eui-Young Choi
Journal: Circulation (2013)

Purpose: Both diastolic dysfunction and neurohormonal activation are important prognosticators in patients with dilated cardiomyopathy (DCM). However, relationship between degree of diffuse extracellular expansion quantified by post-contrast T1 mapping and LV diastolic function and degree of neurohormal activation has not been fully evaluated yet. In this study, we sought to evaluate the relationship between post-T1 value and LV diastolic function and neurohormonal activation assessed by LV mass/volume ratio, echo-Doppler indices and NT-pro BNP level. Methods: Sixty-three patients with DCM who underwent both CMR and echocardiography were enrolled. Post-contrast-15 minutes T1 value was generated from TI scout images obtained by Look-Locker inversion recovery sequence by curve-fitting algorithm. T1 sample volume was obtained in three interventricular septal points and their average T1 value was used for the analysis. NT-proBNP was also measured as a biomarker of LV diastolic stretch in the 43 patients. Resu...