tbuckley/cabot-search huggingface dataset:
Serum Lipoprotein(a) Level Is Related to Thrombin Generation and Spontaneous Intermittent Coronary Occlusion in Patients With Acute Myocardial Infarction
Authors: Agha W. Haider, Felicita Andreotti, Gilbert R. Thompson, Cornelis Kluft, Attilio Maseri, Graham J. Davies
Journal: Circulation (1996)

Background Thrombotic occlusion of the infarct-related coronary artery is often intermittent in the early, evolving phase of acute myocardial infarction. To assess their relationship to this pattern of coronary occlusion, serum or plasma concentrations of cholesterol, triglyceride, lipoprotein(a), and coagulation and fibrinolytic factors were measured in venous blood before the initiation of thrombolytic therapy. Methods and Results Thirty-two patients (23 men, 9 women; age, 30 to 70 years) with acute myocardial infarction received intravenous recombinant tissue plasminogen activator (20 to 60 megaunits) within 6 hours of the onset of symptoms. Continuous ECG ST-segment recording demonstrated intermittent occlusion of the infarct-related coronary artery in 12 patients (group 1) before the start of thrombolytic treatment and persistent occlusion in 20 patients (group 2). Groups 1 and 2 were similar in age, sex, race, duration of symptoms, blood sample collection time, location of the infarct-related coronary artery, and extent of coronary artery disease. The serum level (median [interquartile range]) of lipoprotein(a) was 34 (13 to 47) mg/dL versus 11.5 (5 to 27) mg/dL ( P =.02), and the plasma level (median [interquartile range]) of thrombin–antithrombin III complex was 10.85 (6.4 to 21.5) versus 6.8 (4.2 to 8.7) μg/L −1 ( P &lt;.04) in groups 1 and 2, respectively. The levels of the other factors were similar in both groups. Conclusions The phenomenon of spontaneous intermittent closure and reopening of coronary arteries early during acute myocardial infarction in humans is associated with a higher level of lipoprotein(a) and of a marker of thrombin generation, suggesting that lipoprotein(a) and thrombin are closely related to coronary patency in these patients.
ACCELERATED INHIBITION OF PLATELET AGGREGATION, INFLAMMATION AND MYONECROSIS BY ADJUNCTIVE CILOSTAZOL LOADING IN PATIENTS WITH ACUTE CORONARY SYNDROME: THE RESULTS OF THE ACCEL-LOADING-ACS MULTICENTER RANDOMIZED TRIAL
Authors: Young-Hoon Jeong, Kyounghoon Lee, Sang-Yong Yoo, Jae-Hyeong Park, Jon Suh, Keun-Ho Park
Journal: Journal of the American College of Cardiology (2012)
Corrigendum to “Current strategies in antiplatelet therapy — Does identification of risk and adjustment of therapy contribute to more effective, personalized medicine in cardiovascular disease?” [Pharmacol. Ther. 127(2) (2010) 95–107]
Authors: Tobias Geisler, Meinrad Gawaz, Steven R. Steinhubl, Deepak L. Bhatt, Robert F. Storey, Marcus Flather
Journal: Pharmacology & Therapeutics (2010)
Twenty-five years of preconditioning: are we ready for ischaemia? From coronary occlusion to systems biology and back
Authors: D. Garcia-Dorado, I. Barba, J. Inserte
Journal: Cardiovascular Research (2011)

It was 25 years ago that the phenomenon of ischaemic preconditioning was first described. The protection afforded by preconditioning was found to be exceptionally robust and aroused immediate interest amongst the scientific community. During the last quarter century, a large research effort has been made to elucidate its molecular mechanisms with the final aim of using this knowledge to develop new cardioprotective treatments. The scientific impact of the discovery of ischaemic preconditioning has been huge—it has allowed a change of paradigm in the understanding of ischaemia–reperfusion injury, from being a mere consequence of energy deprivation to being a complex, active process taking place to a large extent during the reperfusion phase. However, the clinical impact has been small, and some have anticipated a loss of interest in preconditioning unless this changes in the near future. We propose that the failure to develop clinical applications from ischaemic preconditioning is due in part to the incomplete understanding of its mechanisms and that a new integrative scientific approach should be used to resolve the complex networks of preconditioning protection signalling.
The role of activin and transforming growth factor-β in the regulation of organ mass in the rat liver
Authors: Kimitaka Kogure, You-Qing Zhang, Akito Maeshima, Keiji Suzuki, Hiroyuki Kuwano, Itaru Kojima
Journal: Hepatology (2000)

The present study was conducted to assess the role of activin(s) in the regulatory mechanism to maintain constant liver mass. To this end, we infused follistatin, an activin antagonist, into the portal vein of the rat. Follistatin induced DNA synthesis, as assessed by bromodeoxy uridine labeling, in intact livers. Small peaks of bromodeoxy uridine labeling were observed after 3 and 18 hours of infusion, and a large peak was observed after 48 hours. In follistatin-treated rats, the DNA content of the liver was significantly elevated after 72 hours and returned to the basal value within 120 hours. Likewise, liver weight increased significantly after 60 and 72 hours, but returned to the control value within 120 hours. Apoptosis of hepatocytes, assessed by the Tdt-mediated, dUTP-biotin nick end labeling method was observed after 72 hours or later. Messenger RNA (mRNA) expression of hepatocyte growth factor, transforming growth factor-α, tumor necrosis factor-α, and interleukin-6 did not increase after the addition of follistatin. The mRNA expression and immunoreativity of transforming growth factor-β increased after the administration of follistatin. These results suggest that the blockade of activin action leads to the initiation of DNA synthesis in the intact liver. Activins may tonically inhibit hepatocyte growth in the intact liver. Transforming growth factor-β may also act to maintain constant liver mass when activin action is blocked.
Angiographic in-stent restenosis patten predicts outcome after gamma vascular brachytherapy
Authors: Costantino O. Costantini, Alexandra J. Lansky, Roxana Mehran, Kazuyuki Shirai, Maria Corral, Mosses Tarawali, Teraza Conway, Brian Proctor, Ecaterina Cristea, George Dangas, Gregg W. Stone, Martin Leon
Journal: Journal of the American College of Cardiology (2003)
Intracrine Androgens and AKR1C3 Activation Confer Resistance to Enzalutamide in Prostate Cancer
Authors: Chengfei Liu, Wei Lou, Yezi Zhu, Joy C. Yang, Nagalakshmi Nadiminty, Nilesh W. Gaikwad, Christopher P. Evans, Allen C. Gao
Journal: Cancer Research (2015)

The introduction of enzalutamide and abiraterone has led to improvement in the treatment of metastatic castration-resistant prostate cancer. However, acquired resistance to enzalutamide and abiraterone therapies frequently develops within a short period in many patients. In the present study, we developed enzalutamide-resistant prostate cancer cells in an effort to understand the mechanisms of resistance. Global gene-expression analysis showed that the steroid biosynthesis pathway is activated in enzalutamide-resistant prostate cancer cells. One of the crucial steroidogenic enzymes, AKR1C3, was significantly elevated in enzalutamide-resistant cells. In addition, AKR1C3 is highly expressed in metastatic and recurrent prostate cancer and in enzalutamide-resistant prostate xenograft tumors. LC/MS analysis of the steroid metabolites revealed that androgen precursors such as cholesterol, DHEA and progesterone, as well as androgens are highly upregulated in enzalutamide-resistant prostate cancer cells compared to the parental cells. Knockdown of AKR1C3 expression by shRNA or inhibition of AKR1C3 enzymatic activity by indomethacin resensitized enzalutamide-resistant prostate cancer cells to enzalutamide treatment both in vitro and in vivo. In contrast, overexpression of AKR1C3 confers resistance to enzalutamide. Furthermore, the combination of indomethacin and enzalutamide resulted in significant inhibition of enzalutamide-resistant tumor growth. These results suggest that AKR1C3 activation is a critical resistance mechanism associated with enzalutamide resistance; targeting intracrine androgens and AKR1C3 will overcome enzalutamide resistance and improve survival of advanced prostate cancer patients.
Abstract 2871: Inhibition of androgen receptor-mediated expression of prostate derived ets transcription factor (PDEF) induces a loss of prostate cancer cell differentiation
Authors: Andrew C. haller, Fengzhi Li
Journal: Cancer Research (2012)

Abstract While inhibition of androgen signaling has shown to extend the lives of many patients, there is a growing concern in the field that androgen ablation may select for a more aggressive and lethal phenotype of prostate cancer. It has long been known that androgen receptor (AR) mediates growth and cellular differentiation. Therefore, inhibition of AR may stem cancer growth, but concurrently cause cells to de-differentiate and gain migratory and invasive properties. Prostate derived ets transcription factor (PDEF) is an AR target gene highly expressed in normal prostate tissue and has shown to be sufficient to mediate terminal epithelial cellular differentiation in the lung and colon. Previous studies in our lab have demonstrated, through retrospective IHC staining of FFPE radical prostatectomy specimens, loss of PDEF expression significantly associated with increased incidence and patients’ shorter metastatic free survival time with early stage prostate cancer. Furthermore, previous studies in the literature have detected the PDEF promoter sequence through AR ChIP-Sequencing and ChIP-on-ChIP experiments. We therefore studied the regulation of PDEF expression by AR as a potential mediator of prostate epithelial cellular differentiation. Our data indicated that anti-androgens, androgen starvation or AR shRNA was sufficient to abrogate PDEF protein and mRNA expression. Stable expression of AR shRNA or PDEF shRNA by lentiviral infection displayed a coordinate decrease in e-cadherin expression and an increase in vimentin expression, indicating a potential shift to a mesenchymal-like phenotype. This epithelial-to-mesenchymal transition was also observed in cells acutely treated with anti-androgens bicalutamide or finasteride. Together, these results demonstrate that androgen ablation therapy may directly drive cells to de-differentiate and gain migratory/invasive capabilities, and therefore should only be indicated for those patients with a very short life expectancy or co-existing morbidities. 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 2871. doi:1538-7445.AM2012-2871
1030. Pyrazolo[3,4-d]Pyrimidine Guanine Base Substitution in Triplex Forming Oligonucleotides Improves Target Specificity and Chromosomal Mutagenesis
Authors: Joanna Y. Chin, Janice A. Lloyd, Faye A. Rogers, Peter M. Glazer
Journal: Molecular Therapy (2006)

Triplex forming oligonucleotides (TFOs) can induce site-specific damage, repair and recombination in episomal and chromosomal targets. However, several limitations preclude their effective use for gene targeting at the present time. For example, purine-rich TFOs have reduced binding in physiologic levels of monovalent cations, especially K+, apparently due to self-association at the guanine N7. We have substituted a 30-mer purine-rich TFO with the base analog 7-deaza-8-aza-guanine (PPG), in which the N7 and C8 positions of the guanine ring are exchanged. We show here that the PPG- substituted TFOs have increased binding affinity to a polypurine target site in vitro, even in the presence of physiologic [K+]. As well, the PPG-substituted TFOs are more efficient at forming covalent crosslinks at a chromosomally integrated target site. Notably, TFOs containing PPG substitutions at every third guanine induced almost a four-fold increase in mutation frequency in a chromosomal reporter gene in mammalian cells, almost twice the rate as a TFO containing natural guanine. In addition, we are interested in using modified TFOs to target disease-related genes in mammalian cells; preliminary results indicate that PPG-substituted TFOs can target an endogenous intronic sequence of the beta-globin locus to promote gene correction. PPG modifications, therefore, can augment triplex specificity and stability, resulting in enhanced gene targeting and correction.
[274] SURVEILLANCE FOR EARLY DIAGNOSIS OF HEPATOCELLULAR CARCINOMA: IS IT EFFECTIVE IN INTERMEDIATE/ADVANCED CIRRHOSIS?
Authors: V. Santi, F. Trevisani, A. Gramenzi, R. Casadio, M.A. Di Nolfo, P. Del Poggio, L. Benvegnu, G. Rapaccini, F. Farinati, M. Zoli, F. Borzio, E.G. Giannini, E. Caturelli, M. Bernard
Journal: Journal of Hepatology (2007)
Early change in bilirubin levels is an important prognostic factor in severe alcoholic hepatitis treated with prednisolone
Authors: Philippe Mathurin, Marcelle Abdelnour, Marie-José Ramond, Nicolas Carbonell, Laetitia Fartoux, Lawrence Serfaty, Dominique Valla, Raoul Poupon, Jean-Claude Chaput, Sylvie Naveau
Journal: Hepatology (2003)

Early identification of patients with severe (discriminant function >or=32) biopsy-proven alcoholic hepatitis (AH) who are not responding to corticosteroids would be clinically relevant. Our goal was to develop simple criteria that will help physicians to promptly identify nonresponders to corticosteroids. A total of 238 patients were included. We used 6 months survival as an end point because of the rule requiring 6 months for listing alcoholic patients for transplantation. Overall survival at 1 and 6 months was 85% +/- 2.3% and 64.3% +/- 3.3%, respectively. An early change in bilirubin levels (ECBL) at 7 days (defined as bilirubin level at 7 days lower than bilirubin level on the first day of treatment) was observed in 73% of patients. At 7 days, in patients with ECBL, bilirubin decreased (84 +/- 75 micromol/L [4.94 +/- 4.40 mg/dL]), whereas it increased in patients without ECBL (76.5 +/- 77 micromol/L [4.50 +/- 4.54 mg/dL], P <.0001). Ninety-five percent of patients with ECBL continued to have improved liver function during treatment. At 6 months, survival of patients with ECBL was significantly higher than that of patients without ECBL, 82.8% +/- 3.3% versus 23% +/- 5.8%, P <.0001. On multivariate analysis, ECBL, discriminant function and creatinine were independent prognostic variables, and ECBL had the most important prognostic value. In conclusion, ECBL is a very simple predictive factor for identifying nonresponders. A recommendation to discontinue corticosteroids after 7 days in patients without ECBL, suggested by our results, awaits additional confirmation.
UK research bodies agree steps to protect anonymity of study participants
Authors: J. Wise
Journal: BMJ (2014)

A group of medical research bodies have agreed to a set of measures to reduce the risk that participants in genomic studies can be subsequently identified.

The Wellcome Trust, Cancer Research UK, the Economic and Social Research Council, and the Medical Research Council have fully accepted the steps set out in October 2013 by the Expert Advisory Group on Data Access.1

The issue was highlighted last year in the journal Science , …
Parents of people with Down's syndrome report suboptimal care
Authors: S. Mayor
Journal: BMJ (1999)

People with Down's syndrome may be receiving suboptimal care because of their condition, suggests a survey published this week by the UK Down's Syndrome Association.

The survey of 1509 parents who belong to the association found that 28%of respondents expressed a high level of dissatisfaction with the medical care that their child had received.

Liz Marder, consultant community paediatrician, Nottingham Community Health NHS Trust, and medical adviser to the association, said: “Incidents reported in the survey …
The Addition of Vitamin D (VitD) to an Intranasal Steroid (INS) Improves Control of Symptoms in Seasonal Allergic Rhinitis (SAR)
Authors: F.M. Baroody, J. Lane, S. Watanabe, M. DeTineo, J. Pinto, R.M. Naclerio
Journal: Journal of Allergy and Clinical Immunology (2012)
Towards complete endoscopic staging of the mediastinum?
Authors: R. Rintoul
Journal: Endoscopy (2006)

Accurate staging of the mediastinum is a critical part of the management for newly diagnosed cases of lung cancer. It is well recognised in non small cell lung cancer (NSCLC) that stage at presentation is the main determinant of survival. Furthermore, the degree of spread will determine the most appropriate and optimal treatment strategy. NSCLC usually metastasises initially via the lymphatic system to locoregional lymph nodes (hilar and mediastinal) and subsequently to distant organs by haematogenous spread.
Construction and Characterization of Novel, Recombinant Immunotoxins Targeting the <i>Her2/neu</i> Oncogene Product: <i>In vitro</i> and <i>In vivo</i> Studies
Authors: Yu Cao, James D. Marks, John W. Marks, Lawrence H. Cheung, Sehoon Kim, Michael G. Rosenblum
Journal: Cancer Research (2009)

Abstract The goal of this study was to characterize a series of anti-Her2/neu immunotoxin constructs to identify how different antibodies and linker choices affect the specificity and cytotoxicity of these proteins. We constructed a series of immunotoxins containing either the human single-chain antibody (scFv) C6.5 or the murine scFv e23 fused to the highly toxic recombinant gelonin (rGel) molecule. Based on the flexible GGGGS linker (L), the fusion construct C6.5-L-rGel was compared with e23-L-rGel to evaluate the specific cytotoxic effects against Her2/neu-positive and Her2/neu-negative tumor cells. Both constructs retained the specificity of the original antibody as well as the biological activity of rGel toxin. The two constructs displayed similar cytotoxicity against different carcinoma cells. We additionally introduced the modified linkers TRHRQPRGWEQL (Fpe) and AGNRVRRSVG (Fdt), which contained furin cleavage sites, to determine the effect of these design changes on stability and cell killing efficiency. The introduction of furin cleavage linkers (Fpe or Fdt) into the molecules resulted in dissimilar sensitivity to protease cleavage compared with the constructs containing the L linker, but very similar intracellular rGel release, cytotoxic kinetics, and induction of autophagic cell death in vitro. Xenograft studies with SKOV3 ovarian tumors were done using various C6.5/rGel constructs. C6.5-L-rGel was more efficient in tumor inhibition than constructs containing furin linkers, attributing to a higher stability in vivo of the L version. Therefore, our studies suggest that human C6.5-L-rGel may be an effective novel clinical agent for therapy of patients with Her2/neu-overexpressing malignancies. [Cancer Res 2009;69(23):8987–95]
The Electrocardiogram in Ventricular Septal Defect
Authors: DENNIS J. VINCE, JOHN D. KEITH
Journal: Circulation (1961)

One hundred and nineteen cases of ventricular septal defect in infancy and childhood have been reviewed, with special reference to the electrocardiogram. The changes in the electrocardiogram were related to the hemodynamics found at cardiac catheterization, and particularly the pulmonary to systemic blood flow ratios, pulmonary artery pressures, and oximetry. They were also studied in relation to the groups of cases that obviously had a low pulmonary vascular resistance with or without diastolic loading of the left ventricle. Survival of a patient following closure of the defect with a drop in pulmonary artery pressure was also taken as a sign that the pulmonary vascular resistance was not excessive. The patients with clinical and hemodynamic evidence of a high pulmonary vascular resistance were also evaluated in relation to the electrocardiogram. The information obtained from the electrocardiogram may be graded according to degree of severity: (a) normal electrocardiogram, (b) left ventricular loading, (c) combined loading, (d) isolated right ventricular loading. These groups may be further graded depending on the diminishing number of signs listed below. 1-7 A detailed review of these four groups in relation to the following criteria may allow one to identify a low or only moderately raised pulmonary vascular resistance, or one that is sufficiently moderate to permit successful corrective surgery in the pediatric age group: 1. An R in V 6 over 20 mm. 2. A Q in V 6 of 4 mm. or over. 3. An S in V 1 over 25 mm. 4. A Q in V 6 of 2 mm. or more when associated with evidence of right ventricular loading. 5. An axis of less than 90°. 6. Counterclockwise vector. 7. Broad notched P waves in standard leads I or II, with late inversion in V 1 . As a rule, several of these criteria occur together, but even if only one of them is present, one may conclude that the pulmonary vascular resistance is not excessive. Further support to this conclusion is evident if any of the above 7 items are accompanied by one or more of the following: (x) a pulmonary blood flow that is twice systemic, (y) an absence of reversal of flow through the defect either at rest or with exercise, (z) an age under 7 years. Among the 119 infants and children with ventricular septal defect, over 90 per cent appeared to have a sufficiently low pulmonary vascular resistance to be operable provided the surgical technic is adequate and provided complete heart block does not occur. Age appears to be an important factor in assessing the likelihood of success at surgery. Only an exceptional case shows hemodynamic findings indicating inoperability before the age of 7 years. During the first year of life many cases of ventricular septal defect have signs of left ventricular loading appear or increase, suggesting a favorable trend in the pulmonary vascular resistance. Until surgical technic makes operation more readily feasible in infancy, the optimum age of correction would appear to be between 2 and 7 years.
Preventive Medicine: What Does It Prevent?
Authors: John J. Whyte
Journal: JAMA (1993)

To the Editor.  —Dr Leaf 1 makes a powerful argument supporting preventive medicine as an essential element of the nation's health care system. His comments still leave critical questions unanswered. Among them are the following:   Leaf states that any impartial examination of the evidence would indicate the need for a major change in the emphasis to embrace cost-effective preventive measures. What realistic means can bring about the substantial cultural changes on the part of both physicians and the  for which he calls, particularly public acceptance of more responsibility individually for their own health through choices they make and the life-styles they pursue?  How should the connections between preventive medicine, public health, and clinical medicine be established so that  ailing health care system becomes disease-prevention and health-promotion oriented?  Our current approach to medical education may not be totally responsible for our ailing health system, but are there no changes