tbuckley/cabot-search huggingface dataset:
Abstract 9406: ST-Segment Elevation in Lead AVR Strongly Predicts Long-Term Adverse Outcomes in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome
Authors: Masami Kosuge, Toshiaki Ebina, Kiyoshi Hibi, Kengo Tsukahara, Noriaki Iwahashi, Nobuhiko Maejima, Eiichi Akiyama, Satoshi Umemura, Kazuo Kimura
Journal: Circulation (2014)

Introduction: In non-ST-segment elevation acute coronary syndrome (NSTE-ACS), ST-elevation in lead aVR (ST↑aVR) on admission ECG has been shown to be associated with severe coronary artery disease, but its impact on long-term clinical outcomes is unclear. Methods: We studied 454 patients with NSTE-ACS who underwent coronary angiography during initial hospitalization. Patients were divided into the 3 groups according to the degree of ST↑aVR on admission ECG: no ST↑aVR (n=301, G-A); ST↑aVR &lt;1.0 mm (n=82, G-B); and ST↑aVR ≥1.0 mm (n=71, G-C). Troponin T (TnT), hemoglobin (Hb), estimated glomerular filtration rate (eGFR), brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), TIMI risk score, and summed ST-segment depression in other leads were also measured on admission. Results: There were no differences in sex or coronary risk factors except for diabetes mellitus in the 3 groups. In G-A, G-B, and G-C, age was 66±11, 68±11, and 70±11 years; the rates of diabetes mellitus were 30%, 48%, and 51%; Killip class ≥2 was 7%, 20%, and 34%; positive TnT was 30%, 46%, and 56%; TIMI risk score was 2.8±1.4, 3.6±1.3, and 3.8±1.2; the levels of Hb were 13.4±1.9, 13.2±1.9, and 12.2±2.3 g/dl; eGFR was 65±24, 59±27, and 53±28 ml/min/1.73 m2; BNP was 155±249, 386±338, and 455±507 pg/ml; hsCRP was 0.339±1.499, 0.654±1.899, and 0.842±1.788 mg/dl; summed ST-segment depression was 2.0±2.6, 5.6±3.5, and 13.0±6.6 mm; the rates of left main or 3-vessel disease were 9%, 44%, and 75%; and major adverse events (death, [re]infarction, urgent revascularization, or heart failure requiring hospitalization) at 5 years were 19%, 43%, and 58%, respectively (all p&lt;0.01). After adjusting for baseline characteristics, multivariate analysis showed that as compared with no ST↑aVR, the hazard ratios (95% CI) for 5-year adverse events associated with ST↑aVR &lt;1.0 mm and ST↑aVR ≥1.0 mm were 2.16 (1.10-5.59; p=0.019) and 3.90 (1.44-9.76; p=0.001), respectively. Conclusions: In patients with NSTE-ACS, greater ST↑aVR on admission ECG strongly predicted 5-year adverse outcomes, even after adjusting for traditional risk factors, biomarker profiles, and ST-segment depression in other leads. Our findings suggest the importance of ST↑aVR in risk stratification for NSTE-ACS.
Hemorrhagic death associated with a high titer factor V inhibitor
Authors: Macie C. Coots, Albert F. Muhleman, Helen I. Glueck
Journal: American Journal of Hematology (1978)

Abstract An acquired bleeding diathesis was first noted in a 51‐year‐old patient 11 days following an exploratory laparotomy. Laboratory studies indicated the cause of bleeding to be the development of a circulating anticoagulant which inhibited factor V activity. The inhibitor, an immunoglobulin of the IgG class, was separated by use of Sephadex G‐200 filtration, disc electrophoresis, and isoelectric focusing. Despite vigorous immunosuppressive, antifibrinolytic, and replacement therapy, including the use of a “prothrombin complex” and plasmaphoresis, the bleeding diathesis could not be reversed and the patient died of hemorrhage. Although inhibitors to factor V are not usually associated with major life‐threatening hemorrhage, this case demonstrates that the development of such an inhibitor can be an ominous finding. The use of an aminoglycoside antibiotic in this and other patients so reported may be one of the contributing causes to the development of such an inhibitor.
Risks of Pregnancy in Women With Cardiac Disease
Authors: Arthur Selzer
Journal: JAMA (1977)

PREVENTIVE cardiology includes not only prevention of development of cardiac disease but also steps to delay progression of existing cardiac conditions, prevention of associated complications, and preservation of cardiac reserve. The cardiologist should provide counsel to patients with cardiac disease regarding occupation, recreational activities, place of habitation, and other environmental factors. A major aspect of preventive cardiology is counseling young women with cardiac disease regarding childbearing. In the absence of a sound data base, it is impossible to provide statistically valid figures regarding the increment of risk of pregnancy for each situation, but a reasonable set of guidelines can be developed for various cardiac lesions affecting women of childbearing age. To provide prepregnancy counseling we need to know (1) the degree of increased cardiac workload as well as other hemodynamic alterations occurring during normal pregnancy, (2) the complications of pregnancy relevant to cardiac disease, and (3) the natural history of
Abstract 3698: Chemopreventive efficacy of pioglitazone on lung cancer in mice
Authors: Yian Wang, Michael James, Weidong Wen, Yan Lu, Eva Szabo, Ronald A. Lubet, Ming You
Journal: Cancer Research (2011)

Abstract Pioglitazone is a ligand of PPARγ nuclear receptor. Activation of PPARγ has been associated with anticancer activities in a variety of cancer cell lines through inhibition of proliferation and promotion of apoptosis. We examined the effect of pioglitazone, which is approved for the treatment of type II diabetes mellitus, on lung cancer development in carcinogen-induced non-small cell lung cancers in mice. When pioglitazone was administered beginning 8 weeks after the first dose of carcinogen treatment, pioglitazone significantly inhibited tumor load (sum of tumor volume per lung in average) by 64% (P &amp;lt; 0.05) in p53(wt/wt) mice and 50% (P &amp;lt; 0.05) in p53(wt/Ala135Val) mice in the lung adenocarcinoma model. Delayed administration of pioglitazone caused a limited (35%, P &amp;lt; 0.05) decrease in lung squamous cell carcinoma. Induction of apoptosis occurred in both model systems. These data show that pioglitazone significantly inhibited progression of both adenocarcinoma and SCC in the two mouse model systems. 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 3698. doi:10.1158/1538-7445.AM2011-3698
Zimbabwean clearance policy leaves 1.5 million people homeless
Authors: Owen Dyer
Journal: BMJ (2005)

The Zimbabwean government's campaign to destroy what it labels illegal settlements is continuing despite international condemnation and the visit of a United Nations' special envoy. Operation Murambatsvina, Shona for “sweep out the rubbish,” is described by President Robert Mugabe as an urban renewal programme but condemned by charities and international observers as retaliation against opposition supporters.

The violent demolition of Zimbabwean shanty towns has left up to 1.5 million people homeless in the middle of winter and forced 300 000 children away from their schools since the campaign was launched on 19 May, according to UN estimates.

Porta Farm, a large suburb of the capital Harare, was bulldozed on …
Israeli army's shoot to kill policy
Authors: Derek A Summerfield
Journal: BMJ (2005)

EDITOR—My personal view last October on the Israeli army operations in the Palestinian territories occupied by Israel, attracted support as well as vilification on bmj.com.1

I noted that two thirds of all Palestinian child fatalities had been caused by small arms fire(from relatively close range), in fully half of the cases to the head or upper torso—the sniper's wound. My statement that “clearly, soldiers are routinely authorised to shoot to kill children in situations of minimal or …
Abstract 5461: Role of the NLRP3 inflammasome in the development and drug resistance of malignant mesothelioma
Authors: Arti Shukla, Jill M. Miller, Jedd M. Hillegass, Maximilian B. MacPherson, Stacie L. Beuschel, Harvey I. Pass, Brooke T. Mossman
Journal: Cancer Research (2012)

Abstract Inflammation plays an important role in development of various cancers including malignant mesothelioma (MM). We have shown that asbestos activates NOD-like receptor protein 3 (NLRP3), a component of the inflammasome in human macrophages. As chronic asbestos exposure is a key risk factor for the development of MM, we hypothesized that inflammasome-mediated inflammation might underlie the pathogenesis of this cancer. To show the involvement of NLRP3 in asbestos-induced mesothelioma, we demonstrated that exposure of asbestos to immortalized human mesothelial cells (LP9/hTERT), a cell type responsible for origin of MM, caused mRNA increase and activation of NLRP3 as measured by caspase-1 activation and IL-1β release. Inhibition of NLRP3 by siRNA caused significant decreases in NLRP3 mRNA levels as well as asbestos-induced IL-1β release in medium. On the other hand, human MM lines and tumor tissues showed significantly decreased levels of NLRP3 and caspase-1 as compared to LP9 or matching normal tissues respectively. Our findings suggest that initial exposure to asbestos causes increased mRNA levels and activity of NLRP3, which may help in MM development by promoting mesothelial cell transformation. However, tumor development culminates in MM with decreased NLRP3 protein and increased drug resistance which may be due to caspase-1 inactivation. Thus NLRP3 may be an appropriate target for therapy of MM, especially in combination with cytotoxic chemotherapeutic drugs and IL-1 receptor antagonists. This study is supported by a Meothelioma Applied Research Foundation (MARF) grant (AS) and by NIEHS grants T32 ES07122 (BM). 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 5461. doi:1538-7445.AM2012-5461
What is segmental neurofibromatosis?
Authors: C. MOSS, S.H. GREEN
Journal: British Journal of Dermatology (1994)

Journal Article What is segmental neurofibromatosis? Get access C. MOSS, C. MOSS Department of Dermatology, Birmingham Children's Hospital, Ladywood Middleway, Ladywood, Birmingham B16 8ET, U.K. Search for other works by this author on: Oxford Academic Google Scholar S.H. GREEN S.H. GREEN Department of Neurology, Birmingham Children's Hospital, Ladywood Middleway, Ladywood, Birmingham B16 8ET, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 130, Issue 1, 1 January 1994, Pages 106–110, https://doi.org/10.1111/j.1365-2133.1994.tb06893.x Published: 01 January 1994 Article history Accepted: 30 June 1993 Published: 01 January 1994
Abstract 2203: AP-1 activation and a functional SNP242 regulates the LY-6K gene expression in human breast cancer cells
Authors: Hyun Kyung Kong, Jong Hoon Park
Journal: Cancer Research (2012)

Abstract Background: Lymphocyte antigen 6 complex locus K(LY-6K), a member of LY-6/uPAR receptor superfamily and cancer-testis antigen, is a novel breast cancer biomarker. Also LY-6K is target antigen for the head and neck squamous cell carcinoma, and lung and esophageal carcinoma. Elevated LY-6K induces cell invasion and metastasis through activating the Raf-1/MEK/ERK signaling pathway. However, the molecular mechanisms that mediate regulation of human LY-6K gene expression are completely unknown. Material and Methods: Within the pGL3-basic reporter vector, the −3050/+182 bp fragment, truncated and mutated fragment upstream of the LY-6K gene was subcloned and measured promoter activity. Subsequently, multiple cis elements were identified using several gene tool software (TFSEARCH, TRANSFAC, PROMO and MATCHTM) in the promoter of human LY-6K gene. We investigated the transcription factor and the effect of single nucleotide polymorphism (SNP) on LY-6K promoter activity and transcription factor binding using chromatin immunoprecipitation (ChIP) assays, electrophoretic mobility shift assays (EMSA), and supershift assays. Results: LY-6K gene was expressed in estrogen receptor (ERα) and progesterone receptor (PR)-negative breast cancer cell lines. A novel AP-1 binding site in the LY-6K promoter regulates LY-6K gene expression. A polymorphic C/G-SNP at the 242 nucleotide position in the promoter region (rs2585175, called SNP242) was validated to be located in a PAX-3 transcription binding motif, which is appear with the presence of the G-allele resulting in a ∼54% decrease in LY-6K promoter activity by interfering binding of AP-1 transcription factor. Discussion: The activity of the AP-1 transcription factor plays an important role in cell mobility of breast cancer cells via the promoting of LY-6K gene expression. LY-6K expression is dependent on not AP-1 transcription factor, but also functional SNP242 G-allele. These results suggested that the polymorphism rs2585175 (SNP242), in close proximity of the LY-6K promoter, lead to LY-6K downregulation, and thus, may reduce the risk of breast cancer. 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 2203. doi:1538-7445.AM2012-2203
Greeks bearing gifts
Authors: A. Dean
Journal: BMJ (1987)

<h3>Introduction</h3> Smoking is a major avoidable cause of ill-health and premature death. Treatments that help patients successfully quit smoking have an important effect on health and life expectancy. Varenicline is a medication that can help smokers successfully quit smoking. However, there are concerns that it may cause adverse effects, such as increase in the occurrence of depression, self-harm and suicide and cardiovascular disease. In this study we aim to examine the effects of varenicline versus other smoking cessation pharmacotherapies on smoking cessation, health service use, all-cause and cause-specific mortality and physical and mental health conditions. <h3>Methods</h3> In this project we will investigate the effects of varenicline compared to nicotine replacement therapies on: (1) long-term smoking cessation and whether these effects differ by area level deprivation; and (2) the following clinically-important outcomes: rate of general practice and hospital attendance; all-cause mortality and death due to diseases of the respiratory system and cardiovascular disease; and a primary care diagnosis of respiratory illness, myocardial infarction or depression and anxiety. The study is based on a cohort of patients prescribed these smoking cessation medications from the Clinical Practice Research Datalink (CPRD). We will use three methods to overcome confounding: multivariable adjusted Cox regression, propensity score matched Cox regression, and instrumental variable regression. The total expected sample size for analysis will be at least 180 000. Follow-up will end with the earliest of either an ‘event’ or censoring due to the end of registration or death. <h3>Ethics and dissemination</h3> Ethics approval was not required for this study. This project has been approved by the CPRD9s Independent Scientific Advisory Committee (ISAC). We will disseminate our findings via publications in international peer-reviewed journals and presentations at international conferences.
TCT-442 The Impact of High Residual Platelet Reactivity After Clopidogrel Loading on Cardiac Mortality in Patients Treated by Percutaneous Coronary Intervention for Chronic Total Occlusion
Authors: Renato Valenti, Rossella Marcucci, Angela Migliorini, Anna Maria Gori, Nazario Carrabba, Betti Giusti, Giampaolo Cerisano, Guido Parodi, Rita Paniccia, Rosanna Abbate, David Antoniucci
Journal: Journal of the American College of Cardiology (2012)
Induction of interleukin-6 by interferon alfa and its abrogation by a serine protease inhibitor in patients with chronic hepatitis C
Authors: N Ito
Journal: Hepatology (1996)

We investigated short-term alterations in plasma interleukin-6 (IL-6), interleukin-1beta (IL-1beta), and tumor necrosis factor alpha (TNF-alpha) levels induced by interferon alfa (IFN-alpha) injection in 18 patients with chronic hepatitis C. A single intramuscular injection of human recombinant IFN-alpha 2a (6 million units [MU]) significantly increased the plasma IL-6 level 6 hours after the injection (P < .05). On the other hand, the IFN-alpha injection did not affect the plasma TNF-alpha and IL-lbeta levels. Polymerase chain reaction (PCR) analysis showed accumulation of IL-6 gene transcripts in peripheral blood mononuclear cells (PBMC) after IFN-alpha injection, indicating that IFN-alpha enhances IL-6 production at the messenger RNA level. The induction of IL-6 by IFN-alpha was completely suppressed by the intravenous administration of gabexate mesilate (GM), a serine protease inhibitor. The mechanism whereby GM suppresses the elevation in circulating IL-6 levels seems to be the inhibition of IL-6 production at the messenger RNA level. Elevations of both serum C-reactive protein (CRP) levels and body temperature after GM-suppressed IFN-alpha injection suggest that the administration of GM by suppressing IL-6 production, may attenuate the IL-6-related responses induced by IFN-alpha injection. In conclusion, we found that IL-6 was induced by IFN-alpha in vivo, and that this induction was completely abrogated by the administration of GM. Our results indicate that serine protease inhibitors may be useful for inhibiting IL-6-relating responses.
Characterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus
Authors: Dimitri Lavillette, Alexander W. Tarr, Cécile Voisset, Peggy Donot, Birke Bartosch, Christine Bain, Arvind H. Patel, Jean Dubuisson, Jonathan K. Ball, François‐Loïc Cosset
Journal: Hepatology (2005)

Because of the lack of a robust cell culture system, relatively little is known about the molecular details of the cell entry mechanism for hepatitis C virus (HCV). Recently, we described infectious HCV pseudo-particles (HCVpp) that were generated by incorporating unmodified HCV E1E2 glycoproteins into the membrane of retroviral core particles. These initial studies, performed with E1E2 glycoproteins of genotype 1, noted that HCVpp closely mimic the cell entry and neutralization properties of parental HCV. Because sequence variations in E1 and E2 may account for differences in tropism, replication properties, neutralization, and response to treatment in patients infected with different genotypes, we investigated the functional properties of HCV envelope glycoproteins from different genotypes/subtypes. Our studies indicate that hepatocytes were preferential targets of infection in vitro, although HCV replication in extrahepatic sites has been reported in vivo. Receptor competition assays using antibodies against the CD81 ectodomain as well as ectopic expression of CD81 in CD81-deficient HepG2 cells indicated that CD81 is used by all the different genotypes/subtypes analyzed to enter the cells. However, by silencing RNA (siRNA) interference assays, our results show that the level of Scavenger Receptor Class-B Type-I (SR-BI) needed for efficient infection varies between genotypes and subtypes. Finally, sera from chronic HCV carriers were found to exhibit broadly reactive activities that inhibited HCVpp cell entry, but failed to neutralize all the different genotypes. In conclusion, we characterize common steps in the cell entry pathways of the major HCV genotypes that should provide clues for the development of cell entry inhibitors and vaccines.
Percutaneous Transluminal Mitral Valvuloplasty Normalizes Baroreflex Sensitivity and Sympathetic Activity in Patients With Mitral Stenosis
Authors: Kazuhiro Ashino, Eiji Gotoh, Shin-ichi Sumita, Akihiko Moriya, Masao Ishii
Journal: Circulation (1997)

Background In patients with mitral stenosis, reduced cardiac output or altered pulmonary hemodynamics may increase sympathetic nerve activity. However, the magnitude of the increase in sympathetic activity in such patients and the effect of valvuloplasty on this activity are unknown. Methods and Results We microneurographically measured muscle sympathetic nerve activity before and after mitral valvuloplasty in 10 patients (mean±SEM age, 48±2 years) with mitral stenosis and in 10 healthy volunteers (47±4 years); hemodynamic variables were also measured. Baroreflex sensitivity was assessed on the basis of the ratio of the change in heart rate or muscle sympathetic activity to the change in mean arterial pressure during intravenous infusion of sodium nitroprusside or phenylephrine. At baseline, muscle sympathetic activity was significantly higher in the patients with mitral stenosis than in the control subjects (42.1±3.2 versus 26.1±3.7 bursts/min, P &lt;.05). However, there was no significant difference between the groups in sympathetic activity at 1 week after valvuloplasty. The reduction in sympathetic activity after valvuloplasty was maintained for ≥6 months and correlated with the increase in cardiac index ( r =.74, P &lt;.05). Baroreflex sensitivity was significantly lower in the patients than in the control subjects, but after valvuloplasty there was no significant difference in baroreflex sensitivity between the groups. Conclusions Sympathetic activity is increased in patients with mitral stenosis. Mitral valvuloplasty in such patients results in early and long-lasting normalization of sympathetic nerve activity, possibly because of an improvement in arterial baroreflex sensitivity.
CD99 inhibits neural differentiation of human Ewing sarcoma cells and thereby contributes to oncogenesis
Authors: Anna Rocchi, Maria Cristina Manara, Marika Sciandra, Diana Zambelli, Filippo Nardi, Giordano Nicoletti, Cecilia Garofalo, Stefania Meschini, Annalisa Astolfi, Mario P. Colombo, Stephen L. Lessnick, Piero Picci, Katia Scotlandi
Journal: Journal of Clinical Investigation (2010)

Ewing sarcoma (EWS) is an aggressive bone tumor of uncertain cellular origin. CD99 is a membrane protein that is expressed in most cases of EWS, although its function in the disease is unknown. Here we have shown that endogenous CD99 expression modulates EWS tumor differentiation and malignancy. We determined that knocking down CD99 expression in human EWS cell lines reduced their ability to form tumors and bone metastases when xenografted into immunodeficient mice and diminished their tumorigenic characteristics in vitro. Further, reduction of CD99 expression resulted in neurite outgrowth and increased expression of β-III tubulin and markers of neural differentiation. Analysis of a panel of human EWS cells revealed an inverse correlation between CD99 and H-neurofilament expression, as well as an inverse correlation between neural differentiation and oncogenic transformation. As knockdown of CD99 also led to an increase in phosphorylation of ERK1/2, we suggest that the CD99-mediated prevention of neural differentiation of EWS occurs through MAPK pathway modulation. Together, these data indicate a new role for CD99 in preventing neural differentiation of EWS cells and suggest that blockade of CD99 or its downstream molecular pathway may be a new therapeutic approach for EWS.
Donor statin treatment protects against severe acute graft-versus-host disease after related allogeneic hematopoietic cell transplantation
Authors: Marcello Rotta, Barry E. Storer, Rainer F. Storb, Paul J. Martin, Shelly Heimfeld, Amanda Peffer, David G. Maloney, H. Joachim Deeg, Brenda M. Sandmaier, Frederick R. Appelbaum, Marco Mielcarek
Journal: Blood (2009)
Forming the network—gap junctions in the cardiovascular system
Authors: S Dhein
Journal: Cardiovascular Research (2004)

Cells live together, but die singly,'' Engelmann wrote more than a century ago.Actually, this sentence describes very clearly the function of intercellular communication.Intercellular communication is maintained by gap junctional channels that connect neighboring cells and allow electrical and metabolic communication, thus forming a functional syncytium instead of a simple agglomeration of cells.Gap junctional channels are dodecameric channels