tbuckley/cabot-search huggingface dataset:
FEASIBILITY OF OPTICAL CORONARY TOMOGRAPHY IN QUANTITATIVE MEASUREMENT OF CORONARY ARTERIES WITH LIPIDIC PLAQUE
Authors: Yosuke Katayama, Yasutsugu Shiono, Makoto Orii, Takashi Yamano, Yoshiki Matsuo, Yasushi Ino, Yasushi Ino, Tomoyuki Yamaguchi, Takashi Kubo, Atsushi Tanaka, Syusaku Shioji, Toshikazu Hashizume, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2015)
Mechanical manifestations of activation in cardiac muscle.
Authors: L E Ford
Journal: Circulation Research (1991)

W hen a muscle is stimulated electrically, its ability to contract rises and then falls.It is conceptually easy to imagine, therefore, that something called the "active state" might rise and fall with a well-defined time course.Although the concept is simple, the attempts to measure this time course have produced such conflicting results that the whole concept has fallen into disrepute.1These conflicting results generally are attributed to the fact that the perturbations used to make the measurements frequently altered the active state.Another good reason is that many different parame- ters were being measured as a reflection of the active state, and some of them may have been inappropri- ate.As a result, the terms "active state" and "activation" became imprecise and vague, even though they have remained in general use and embody a potentially useful concept.As the concept of active state became more impre- cise, interest among muscle physiologists shifted away from this area to studies of the individual mechanisms responsible for activation.These newer studies were made possible by the development of chemical techniques that permitted the exploration of molecular mechanisms.Many of these mecha- nisms now have been elucidated, and the first pur- pose of this review is to describe them.This description leads to a definition of what is meant, and what is not meant, by the term "activation."The second, and major, purpose of this review is to examine the changes in contractile properties of mus- cle that accompany changes in activation.In the course of this examination, an effort will be made to define mechanical parameters that signal changes in activation.As with the first section, emphasis will be given to showing that some parameters do not accu- rately signal changes in activation.
The Prevention of Thromboembolism in Acute Coronary-Artery Disease
Authors: David Littmann
Journal: New England Journal of Medicine (1952)

PRESENT treatment of coronary thrombosis includes, almost without fail, some prophylactic measure intended to prevent thromboembolic complications. This normally consists of one of the coumarin derivatives, heparin or a combination of these drugs. By these methods mortality has been cut approximately by half and thromboembolism to at least an equal degree.1 2 3 The inescapable conclusions are that all such patients should receive anticoagulants. An occasional report, however, suggests that not all victims of myocardial infarction need be so treated. Russek and his co-workers,4 for example, believe that it is possible to select the dangerously ill patients with a predictably high incidence . . .
Abstract 743: Assessment of novel tyrosine-chlorambucil hybrid molecules on a panel of breast, ovarian, and uterine cancer cell lines
Authors: Valerie Leblanc, Caroline Descoteaux, Sophie Parent, Gervais Berube, Eric Asselin
Journal: Cancer Research (2010)

Abstract Site-specific drug targeting is the suject of very intense research to improve selectivity and therapeutic index towards breast and gynecological (ovarian and endometrial) cancers. Recently, our group have designed and synthesized a new class of amino acid-linked nitrogen mustard hybrids. The new hybrids are designed to mimic 17β-estradiol in order to target ERα-overexpressing tumor cells. For this purpose, tyrosine was used as the starting material to which chlorambucil was added to construct several tyrosine-chlorambucil hybrids. The phenol group of the tyrosine moiety imitates the phenol group of estradiol. Thus, the new hybrids are designed to target the estrogen receptor and to direct the cytotoxic moiety to hormone-dependent cancer cells. Chlorambucil is a slow acting nitrogen mustard mainly used in chronic lymphocytic leukemia and primary macroglobulinemia. It is also useful in treating lymphosarcoma and Hodgkin's disease. Two different families of hybrids were made. The aim of the study was to determine the cytotoxic effects of these unique molecules using estrogen dependent (ER+; Ishikawa, Ovcar-3, MCF-7, ZR-75-1) and independent (ER-; Hec-1A, A2780, MDA-MB-468) human breast, ovarian and uterine cancer cells. The results show the possible interactions of the two families of hybrids with ERα as demonstrated by molecular modeling. The biological activity of these compounds was evaluated in vitro using the MTT cell proliferation assay. Depending of the different hybrids tested the novel compounds generally possess up to 10 time higher biological activities when compared to the parent drug. Given the significant cytotoxic activity of these original tyrosine-chlorambucil hybrids, we believe that they represent a promising alternative treatment for hormone-dependent female cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 743.
Abstract 4301: Transformation by the D816V mutant of c-Kit is dependent on the PI3-kinase isoform p110δ but independent of its lipid kinase activi.
Authors: Jianmin Sun, Sofie Mohlin, Alicia Lundby, Ulf Hellman, Sven Påhlman, Jesper V. Olsen, Lars Rönnstrand
Journal: Cancer Research (2013)

Abstract Gain-of-function mutations of the receptor tyrosine kinase c-Kit are frequently seen in several malignanices with the D816V mutation being the most common. In this study we demonstrate that a mutant of c-Kit/D816V that is deficient in binding of the p85 subunit of PI3-kinase (M724A) has lost its ability to induce ligand-independent cell survival and proliferation while c-Kit/D816V induced PI3-kinases activity was only marginally reduced. Furthermore, inhibitors of PI3-kinase were unable to block c-Kit/D816V-induced cell survival. These data suggest that PI3-kinase plays a role in c-Kit/D816V induced cell transformation which is independent of its lipid kinase activity. By mass spectrometry, we identified a heavily tyrosine-phosphorylated 110 kDa protein associated with p85 to be the p110δ subunit of PI3-kinase and the site of phosphorylation as Tyr 523, and the phosphorylation is not dependent on the lipid kinase activity of PI3-kinase. Knockdown of p110δ in c-Kit/D816V expressing Ba/F3 cells led to reduced cell survival and proliferation while the PI3-kinase activity remained almost intact. The c-Kit/D816V expressing Ba/F3 cells lost their ability to form colonies in semi-solid culture if p110δ was knocked down. Additionally, knockdown of p110δ λεδ τo ρεδυχεδ τυμoρ σιζε, τυμoρ ωειγητ ανδ blood vessel formation ωηεν c-Kit/D816V expressing Ba/F3 cells were subcutaneously injected into nude mice. Taken together, these results suggest a kinase independent role of p110δ in the D816Vmutant of c-Kit mediated cell transformation and suggest that p110δ could potentially be a selective therapeutic target for c-Kit/D816V expressing tumors. Citation Format: Jianmin Sun, Sofie Mohlin, Alicia Lundby, Ulf Hellman, Sven Påhlman, Jesper V. Olsen, Lars Rönnstrand. Transformation by the D816V mutant of c-Kit is dependent on the PI3-kinase isoform p110δ but independent of its lipid kinase activi. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4301. doi:10.1158/1538-7445.AM2013-4301
Ga-67 and Tc-99m HMPAO Labeled WBC Imaging in Erythema Nodosum Leprosum Reaction of Leprosy
Authors: NAN-JING PENG, JEN-HSIAN WANG, SHIH-PENG HSIEH, GANG-HONG JAO, DAW-GUEY TSAY, REN-SHYAN LIU
Journal: Clinical Nuclear Medicine (1998)

Erythema nodosum leprosum (ENL) occurs in patients with high bacterial loads of leprosy and more than 50 percent of patients have this complication within the first year of effective antileprosy treatment. In a patient with lepromatous leprosy with an ENL reaction, Ga-67 imaging revealed multiple patchy accumulations of tracer in the skin of the face, trunk, arms, and thighs. Tc-99m HMPAO labeled WBC imaging showed no abnormal uptake in those areas. We learned from this case that Ga-67 imaging could detect inflammatory changes of an ENL reaction of leprosy. Tc-99m HMPAO labeled WBC imaging does not appear to be useful in this application.
Abstract 190: Long noncoding RNA XY11-10-11 regulates proliferation and migration of esophageal adenocarcinoma cells
Authors: Xue Yang, Wenjing Wu, Nathaniel Margolies, Jee Hoon Song, Yulan Cheng, Stephen J. Meltzer
Journal: Cancer Research (2012)

Abstract Esophageal carcinoma is one of the most common types of cancer, ranked among the top eight causes of cancer death worldwide. The molecular mechanisms underlying esophageal cancer are very complicated and have not yet been completely clarified. In recent years, long noncoding RNAs (lncRNAs) have been shown to play critical regulatory roles in various cancer biology, yet their potential involvement in esophageal cancer is not well understood. Here, we identified a set of lncRNAs that are differentially expressed in esophageal cancer tissues in comparison to the normal tissues using quantitative real-time polymerase chain reaction. A new lncRNA, which we name XY11-10-11, is significanty increased in expression in human esophageal adenocarcinoma tissues and cell lines. XY11-10-11 is an intergenic lncRNA expressed from a locus located on chromosome 14. Importantly, knockdown of XY11-10-11 by siRNA resulted in inhibition of proliferation and migration in esophageal adenocarcinoma cells (EACs). Moreover, patients with high XY11-10-11 expression levels had a relatively poorer prognosis. Our findings indicate that XY11-10-11 may play a significant role in the development or progression of esophageal adenocarcinoma and may be an potential biomarker for diagnosis and therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 190. doi:1538-7445.AM2012-190
An educational booklet for patient-centred health education about a non-communicable disease in low-income and middle-income countries
Authors: Trishul Siddharthan, Faith Nassali, Robert Kalyesubula, Steve Coca, Asghar Rastegar, Tracy Rabin, Felix Knauf
Journal: The Lancet Global Health (2016)

Background Of all deaths from non-communicable diseases (NCDs), 80% occur in low-income and middle-income countries (LMIC), which makes these countries a key focus for prevention and management of chronic disease. Patient-centred education empowers patients to participate in medical decision making and has been shown to improve health outcomes and quality of life for patients with chronic diseases. However, little is known about its effectiveness in LMICs. In this study, we aimed to implement and measure the effect of a patient-centred intervention in people with heart failure in Kampala, Uganda.
SP0162 The Monocyte-Macrophage System and the Influence of Cytokines/CSFS
Authors: J. Hamilton
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Monocyte/macrophage lineage development and function in the steady state and during inflammation are heavily influenced by cytokines, including macrophage-colony stimulating factor (M-CSF or CSF-1) and granulocyte macrophage-CSF (GM-CSF). In the steady state, CSF-1 controls the development of certain populations of tissue macrophages and blood monocytes, as well as specific dendritic cell (DC) subsets, while another CSF-1 receptor ligand, IL-34, does so for microglia and epidermal Langerhans cells; on the other hand, GM-CSF controls the normal development of alveolar macrophages and certain gut and skin DC populations. With respect to inflammation and host defense, macrophage populations have been categorised for convenience into M1 and M2 "polarization" and/or "activation" states following cytokine treatment, an approach which of necessity is simplistic in nature. The respective contributions of GM-CSF and CSF-1 to macrophage lineage "activation" or phenotypes is discussed as is the data resulting from their in vivo blockade in models of inflammation/autoimmunity. <h3>Disclosure of Interest</h3> None Declared
THU0179 Prevalence, etiology and risk factors for pulmonary arterial hypertension in a cohort of patients with lupus
Authors: I. Rúa-Figueroa, F. Leόn, A.Gª Quintana, S. Ojeda, F. Francisco, M.Gª Bello, P. Cabrera, N. Ojeda, J. Pulido, A. Naranjo, J. Ortega, G. P-Peñate
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pulmonary hypertension (PHT) has been reported between 0.5 and 14% in systemic lupus erythematosus (SLE), but some studies have suggested that a mild degree of PHT may be more common. Only a few studies have been carried out in caucasian using an algorithm for systematic evaluation with confirmation by right heart catheterization (RHC). <h3>Objectives</h3> To assess the prevalence, etiology and risk factors for PHT in a monocentric SLE cohort. <h3>Methods</h3> Prospective cross-sectional study of 158 SLE patients (ACR 1997 criteria). Resting doppler echocardiographic (dEcho), diffusing capacity for carbon monoxide (DLCO), NT-proBNP and Borg scale (for dyspnea) was performed in all patients. An exercise test (ET) was conducted in selected patients. We confirm PHT using RHC in the case of sPAP ≥45 mmHg (dEcho) or a +ET (&gt;20mmHg increase in PAPs), excluding patients with obvious cardiac disease. A mean pulmonary pressure &gt;20 mm Hg was accepted as PHT. Cumulative clinical characteristics were collected and damage (SLICC/ACR/DI) (SDI) and severity (Katz index) (IGK) were calculated. <h3>Results</h3> Mean age: 45 (±12.9) years,94.3% females. Mean SLE duration: 14 (±8.0) years; mean SDI:1.1 (±1.6), IGK: 3.3 (±2.25), smokers any time: 37.2%. 21 patients (13.4%) had dyspnea at the evaluation time. 11 patients (6.9%) were found to have any degree of PAH. Etiologic classification (Dana Point 2008): 3 patients have left cardiac disease and the diagnosis was echocardiographic-based (sPAP&gt;35mmHg), 1 patient had resting and 3 had postcapillary PAH on ET, a total of 7 patients in group 2. 1 patient had thromboembolic d. (group 4). 3 patients (2.5%) had precapillary PAH related with SLE (group 1), two of them had been previously diagnosed. Other conditions associated with PAH were not found. All 11 patients (100%) with PAH had dyspnea vs. 10 of 146 (6.8%) without PAH (p&lt;0.001). PAH patients had more impaired DLCO when comparing with patients without PHT: 59% (±14%) vs. 68% (±15%) (p=0.048). 54% of PAH patients vs 4.1% of controls had Nt-proBNP &gt;395, (p=0.000). Difference in medium Nt-proBNP (8685±663 vs. 191±578), p=0.000 (U Mann-Whitney) was also statistically significant. As expected, cardiac disease was more prevalent among PAH patients: 27.3 vs. 6.8%, p=0.05. There were no differences in SLE clinical characteristics between SLE patients with vs. without PHT. <h3>Conclusions</h3> Our data confirms the low prevalence of precapillary PHT in SLE. We found a clear preponderance of cardiac etiology, mainly detected using exercise testing. A HTP screening program based on echocardiography, Nt-proBNP and DLCO not seem to be cost-effective and should be restricted to SLE patients with unexplained dyspnea. <h3>Disclosure of Interest</h3> None Declared
MORTALITY AND CARDIOVASCULAR EVENTS AMONG RELATIVES TO PROBANDS WITH LOW-DENSITY LIPOPROTEIN RECEPTOR MUTATION-VERIFIED FAMILIAL HYPERCHOLESTEROLEMIA: A 20-YEAR COHORT STUDY
Authors: Kasper Aalbæk Kjærgaard, Morten Christiansen, Morten Schmidt, Morten Smærup Olsen, Henrik Jensen
Journal: Journal of the American College of Cardiology (2016)
P134 Sensitisation To Cross-reactive Carbohydrate Determinants In Britain's Bakers: The Implications For Health Surveillance
Authors: H. Harrison, J. Welch, S. Schofield, J. Cannon, B. Fitzgerald, M. Jones
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> The diagnosis of baker’s asthma as part of health surveillance schemes in some UK supermarkets relies on determining sensitisation to wheat flour and/or alpha amylase. Recently, data have emerged suggesting that serum IgE analysis in bakers may be complicated by the presence of clinically irrelevant specific IgE to cross-reactive carbohydrate determinants (CCDs), which are complex-type Asn (N)-linked glycan structures commonly formed in plants. Potentially this might lead to false positive flour specific IgE assays, which would have an impact on bakers undergoing surveillance. The aim of this study was to identify the prevalence of CCD sensitisation in UK bakers and investigate the impact of CCD specific IgE within a health surveillance setting. <h3>Methods</h3> Serum samples from UK bakers attending our occupational asthma clinic (n = 209) were analysed for specific IgE to CCD (MUXF<sup>3</sup>) using ImmunoCAP assay (Phadia). Any positive samples were further tested for specific IgE to grass pollen, and competitive inhibition assays were used to determine cross-reactivity between CCD, flour and grass pollen. <h3>Results</h3> Sensitisation rates to CCD in our population of UK bakers were low (7%) despite high sensitisation rates to grass pollen (48%) and flour (60%). Sensitisation to CCD was more prevalent in those sensitised to either flour or grass than in those not sensitised to flour (11.5% vs 0%, p &lt; 0.001) or grass (10.9% vs 2.8%, p = 0.025). We observed cross reactivity between flour and grass pollen and competitive inhibition assays between CCD and flour or grass pollen revealed cross-reactivity in some but not all sensitised bakers. <h3>Conclusions</h3> Our study demonstrated that a minority of bakers were sensitised to CCD and, interestingly, this was associated with being co-sensitised with both flour and grass. It is unlikely that CCDs have major implications for the health surveillance for UK bakeries. In the minority of bakers with CCD specific IgE, there was some suggestion that CCDs may play a role in the cross-reactivity between flour and grass pollen, although in others it was less likely. Within the clinical setting, it may be prudent to measure CCD specific IgE in bakers who are co-sensitised to both flour and grass pollen.
Increased Absenteeism from Work after Detection and Labeling of Hypertensive Patients
Authors: R. Brian Haynes, David L. Sackett, D. Wayne Taylor, Edward S. Gibson, Arnold L. Johnson
Journal: New England Journal of Medicine (1978)

A study of hypertension in an industrial setting allowed us to confirm and explore an earlier retrospective finding that the labeling of patients as hypertensive resulted in increased absenteeism from work. After screening and referral, we found that absenteeism rose (mean ±1 S.E.) 5.2±2.3 days per year (P<0.025); this 80 per cent increase greatly exceeded the 9 per cent rise in absenteeism in the general employee population during this period. The main factors associated with increased absenteeism were becoming aware of the condition (P<0.01) and low compliance with treatment (P<0.001). Subsequent absenteeism among patients unaware of their hypertension before screening was not related to the degree of hypertension, whether the worker was started on therapy, the degree of blood-pressure control achieved or exposure to attempts to promote compliance. These results have major implications for hypertension screening programs, especially since absenteeism rose among those previously unaware of their condition, regardless of whether antihypertensive therapy was begun. (N Engl J Med 299:741–744, 1978)
Abstract 1251: A role for lactate dehydrogenase in the c-Met/HGF signaling axis
Authors: Alana L. Gray, Filippo Minutolo, James A. Cardelli
Journal: Cancer Research (2012)

Abstract Tumor cells often display a glycolytic phenotype, even in the presence of oxygen; a phenomenon known as the Warburg effect. The ability of cancerous cells to perform aerobic glycolysis is unique when compared to non-cancerous cells, and therefore, presents a possible therapeutic target for elimination of cancer cells that rely on aerobic glycolysis. Activation of the receptor tyrosine kinase, c-Met, by hepatocyte growth factor (HGF) is a major contributing event in the progression of prostate cancer (PCa). Signaling through this receptor leads to increased cell motility, proliferation, invasion and metastasis. Studies have shown that targeting this signaling axis can greatly reduce the number of bone metastases that arise from primary PCa tumors. Oxamate, a lactate dehydrogenase (LDH) inhibitor, and 2-deoxyglucose (2-DG) are known glycolytic inhibitors. Our studies have found that oxamate reduced c-Met activation and HGF-induced cell motility, while 2-DG had no effect. In order to confirm that oxamate was targeting LDH-A or LDH-B, we created LDH-A, LDH-B, and LDH-A/B knockdown (KD) DU145 cells. Although all of the clones used in the experiments had greater than 70% KD, we were unable to recapitulate the effects seen with oxamate. We believe that this could be due to incomplete KD. In support of this, use of a specific LDH-A (πFly-21) inhibitor significantly reduced c-Met activation and HGF-induced cell motility. Together, these data support a role for LDH-A in facilitating HGF-induced c-Met activation. Because oxamate is a direct LDH inhibitor, we hypothesized that oxamate would have a greater reduction in lactate (LA) export from cells than 2-DG; however, both, oxamate and 2-DG reduced LA production by approximately 75% in DU145 prostate cancer cells. Therefore, the ability of oxamate to reduce c-Met activation is not apparently due to a decrease in LA export. However, it is possible that LA import via monocarboxylate transporter 1 (MCT1) activity may be important for c-Met activation and downstream signaling events. In support of this, KD of MCT1 resulted in reduced c-Met activation and blocked HGF-induced cell motility. These data indicate a potential connection between LDH activity/lactate import and the c-Met signaling axis, suggesting that inhibition of these processes may be a new mechanism for preventing c-Met driven metastatic events. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1251. doi:1538-7445.AM2012-1251