tbuckley/cabot-search huggingface dataset:
Abstract 4009: Endothelial Dysfunction has Great Impacts on the Development of Acute Coronary Syndrome and Fatal Cardiovascular Events
Authors: Tatsuaki Murakami, Ikuo Moriuchi
Journal: Circulation (2008)

Endothelial dysfunction is thought to contribute to atherothrombogenic process, however we identify little about practical relationship between clinical evolution of acute coronary syndrome (ACS) and endothelial dysfunction. This study investigated whether endothelial dysfunction has clinical impact on development of ACS. Endothelial dysfunction was graded by ultrasonic measured reactive changes in lumen diameter of right brachial artery following transient forearm occlusion for 5 minutes (FMD; flow-mediated endothelium-dependent vasodilation) in consecutive 518 patients with suspected coronary artery disease. The enrolled patients were categorized into three groups according to the values of FMD, and their cardiovascular events were prospectively followed-up for no less than 36 months. For a mean follow-up period of 60 months with 100% follow-up, the patients with severe endothelial dysfunction (FMD&lt;4%; Group-L, n=174), more frequently developed ACS than Group-M with mild endothelial dysfunction (4%≤FMD&lt;8%, n=171) plus Group-H with preserved endothelial function (FMD 8% or more, Group-H, n=173) (p&lt;0.001, by Kaplan-Meier analysis] and majority of the patients with fatal cardiovascular events belonged to group-L. Cox proportional hazard model analysis showed that severe endothelial dysfunction was the most powerful predictor for future development of ACS (hazard ratio=5.77, 95%confidential interval; 2.52–13.22, p&lt;0.001) and fatal cardiovascular events (hazard ratio=10.34, 95%confidential interval; 1.26 –72.25, p=0.022). These results suggest endothelial dysfunction plays important roles on development of ACS and fatal cardiovascular events in the near future, and strategies based on practical status of endothelial function are required to prevent ACS and fatal cardiovascular events. Cumulative Incidence
Abstract 1708: Decreased S-Nitrosylation of Tissue Transglutaminase Contributes to Age-Related Increases in Vascular Stiffness
Authors: Eric C Tuday, Jae Hyung Kim, Phillip Dowzicky, Helena Cortes, Sungwoo Ryoo, Koenraad Vandegaer, Daniel Nyhan, Marc Halushka, Nicholas A Flavahan, Dan E Berkowitz, Lakshmi Santhanam
Journal: Circulation (2008)

Vascular aging is marked by an increase in vascular stiffness. Tissue-type transglutaminase (tTG) enzymatically forms crosslinks between extracellular matrix proteins and may contribute to this pathobiology. Recently, it has been demonstrated that s-nitrosylation of cysteine residues within the enzyme leads to its inhibition. We hypothesize that tTG is more active in the aging vasculature due to decreased bioavailability of nitric oxide (NO) and impaired S-nitrosylation. tTG activity in aorta measured by the incorporation of biotin labeled pentylamine, a tTG substrate, into crosslinks was markedly increased in old (O) animals compared to young (Y) (3.2 fold increase, n = 6, p = 0.0018). S-nitrosylation of tTG, as determined by the biotin switch assay, was significantly reduced in O vs. Y rat aorta. tTG specific (ϵ-(γ-glutamyl)lysine) crosslinks measured by immunofluorescent staining was significantly increased in O vs Y rat aortic rings. Denitrosylation of tTG in Y rats with DTT increased tTG activity by 41% as did the NOS-inhibitor L-NAME. Treatment of O rats with cystamine (tTG inhibitor) lead to a decrease in vascular stiffness as measured by pulse wave velocity (5.55 ± 0.11 m/s to 4.99 ± 0.22 m/s, n = 6, p = 0.038). Given that tTG nitrosylation is likely NOS-3 dependent, we measured tTG activity and function in NOS-3 −/− mice. tTG activity was significantly increased in NOS-3 −/− vs. WT mice (18.94 ± 0.70 RU vs. 31.63 ± 2.06 RU, n = 4, p = 0.015). Treatment of NOS-3 mice with cystamine decreased aortic stiffness and increased carotid artery compliance. Finally, tTG activity in old human aortic tissue (collected post-mortem) is increased by 30% compared to young despite unchanged protein abundance. These data suggest that NOS-3 dependent NO constrains the activity of tTG by S-nitrosylation of the enzyme. Furthermore decreased NO bioavailability contributes to tTG mediated increases in vascular stiffness. Finally tTG promises to be a critical target in age-related vascular stiffness.
Revascularization for Unprotected Left Main Disease
Authors: David E. Kandzari, Antonio Colombo, Seung-Jung Park, Carl L. Tommaso, Stephen G. Ellis, Luis A. Guzman, Paul S. Teirstein, Corrado Tamburino, John Ormiston, Gregg W. Stone, George D. Dangas, Jeffrey J. Popma, Theodore A. Bass
Journal: Journal of the American College of Cardiology (2009)
Abstract 15817: Tricuspid Valve Imaging by 3D Transesophageal Echocardiography: Feasibility of Coaptation Length Measurement and Its Relationship With Severity of Regurgitation
Authors: Kikuko Obase, Lynn Weinert, Victor Mor-Avi, Roberto M Lang
Journal: Circulation (2014)

Background: The coaptation length (CL) of the mitral valve leaflet decreases with increasing mitral regurgitation. Visualization of the CL of the tricuspid valve (TV) is challenging using conventional 2D echocardiography. The aims of this study were: (1) to test the feasibility of visualizing and quantifying the CL of the TV using three-dimensional (3D) transesophageal echocardiography (TEE), and (2) to study it relationship with the severity of tricuspid regurgitation (TR). Methods: Full-volume 3D TEE datasets of the TV were obtained in 24 patients from the transgastric approach. Using multiplanar reconstruction, short-axis plane depicting an en-face view of the TV was used to mark the central coaptation point (Fig. A). Three planes cutting through this point were then selected to view the 3 coaptation lines between: (1) anterior and posterior, (2) septal and anterior, and (3) septal and posterior TV leaflets (Figs. B-D). The CL was measured in each of these planes to obtain mean CL. The severity of tricuspid regurgitation was graded qualitatively as “none”, “trace”, “mild” and “moderate”. Results: Visualization of leaflet coaptation was feasible in 17/24 patients (71%). The mean CL was 0.89±0.03 cm in patients with no TR (N=4), 0.64±0.13 with trace TR (N=6), 0.50±0.07 with mild TR (N=3) and 0.13±0.11 with moderate TR (N=4). Since there was no overlap between the “moderate” group and the other 3 groups, the threshold of average CL for moderate TR was estimated to be between 0.25 (highest value in the “moderate” group) and 0.39 cm (lowest value in the other groups) (Fig. E). Conclusion: Visualization of the TV leaflet coaptation length from transgastric 3D TEE images is feasible in the majority of patients. TV coaptation length is inversely related to the severity of TR. The ability to visualize and quantify the CL of the TV may be useful when planning tricuspid valve repair surgery. Our findings suggest that CL below the threshold may indicate clinically significant TR.
Evaluation of a Regional Pilot Program to Prevent Mother-Infant HIV Transmission--Thailand, 1998-2000
Authors: Thaineua, Kanshana S, Thewanda D, Amornwichet P, Kullerk N
Journal: JAMA (2001)

This evaluation report summarizes an evaluation of the 2-year pilot program in Thailand initiated by the Ministry of Public Health in 1998-2000.  The program was created to prevent mother-to-infant HIV transmission in a rural area in northeastern Thailand.  It also highlights the rapid translation of research findings into a national public health prevention program in developing countries.  The program involved the integration of routine antenatal counseling and voluntary confidential HIV testing into public antenatal clinic services.  In addition HIV-infected women were offered zidovudine and free powdered infant formula for 12 months.  Assessment of the programs coverage acceptability and impact involved an interview with women whose HIV status was not documented at delivery and with HIV-infected women.  Meanwhile HIV polymerase chain reaction tests were used to assess the programs effectiveness in preventing HIV transmission.  Overall the findings have indicated the high acceptance of HIV testing and adherence to zidovudine as well as reduction of HIV transmission.  Moreover the findings demonstrate the feasibility of implementing programs for the prevention of mother-infant HIV transmission on a large scale in the country.
Controversies in Treatment: How can hospitals ration drugs? Drug rationing in a teaching hospital: a method to assign priorities
Authors: F Bochner, E D Martin, N G Burgess, A A Somogyi, G. M H Misan
Journal: BMJ (1994)

Controversies in TreatmentHow can hospitals ration drugs?When drug budgets are unable to accommodate all new drug requests, a dilemma arises when additional funds become available-which drugs should receive priority?The drug committee at Royal Adelaide Hospital devised a scheme, which they describe here, to rank drug requests to obtain the greatest benefitfor the most patients for each dollar spent.We asked a health economist, a clinical pharmacologist, and a moral philosopher to give their perspectives on this form of rationing, and we then gave the authors an opportunity to respond.
Abstract 1517: Remodeling of Ion-Channel Expression and Cellular Electrophysiology of Cardiac Purkinje Fibers by Heart Failure
Authors: Ange Maguy, Sabrina Lebouter, Philippe Comtois, Denis Chartier, Louis Villeneuve, Stanley Nattel
Journal: Circulation (2008)

Purkinje fibers (PFs) play a key role in cardiac conduction and arrhythmogenesis. Heart failure (HF) causes extensive electrical remodeling. HF-induced changes in atrial and ventricular ion channel subunit expression have been well characterized, but little is known about HF-induced ion channel subunit remodeling and functional consequences in PFs. This study assessed ion channel subunit expression, action potential (AP) properties and conduction in cardiac PF false tendons from control and HF dogs. HF was induced by 2 wk ventricular tachypacing (240 bpm). Control and HF PFs were fast-frozen for ion channel subunit mRNA (RT-qPCR) and protein (Western Blot, immunohistochemistry) assessment. APs were studied with standard micro-electrodes. HF significantly downregulated mRNA expression of subunits involved in AP propagation (Nav1.5, by 56%**, **P&lt;0.01; Cx40, by 66%**, Cx43, by 56%**), automaticity (HCN2, by 75%**; HCN4, by 78%**) and repolarization (Kv4.3, by 43%*, *P&lt;0.05; minK, by 31%*). No significant changes occurred in KChIP2, KvLQT1, ERG, Kir2.1 or Kir3.1/3.4 mRNA. At the protein level, significant downregulation was seen for Nav1.5 (by 38%**), Kv4.3 (by 42%**), HCN4 (by 74%*), Cx40 (by 53%**) and Cx43 (by 30%**). Immunohistochemistry revealed reduced Cx40 and Cx43 expression at PF intercalated disks. AP analysis showed changes consistent with observed decreases in I to and I Na subunits: HF decreased phase 1 slope (by 56%**), AP overshoot (by 32%*) and dV/dt max (by 35%*). AP properties associated with unchanged subunits (eg, resting potential, overall AP duration) were unaltered. Because of consistently significant changes in subunits governing impulse propagation (Nav1.5, Cx40, Cx43), we examined HF effects on AP propagation in PF false tendons with dual microelectrodes: conduction velocity decreased from 2.2±0.1 m/s (control) to 1.5±0.1 m/s* (HF). We have characterized for the first time HF effects on ion-channel subunit expression in cardiac PFs, finding prominent alterations in a variety of important subunits that control AP repolarization and propagation. These changes in PF ion-channel subunits likely contribute to conduction disturbances and arrhythmogenesis in the failing heart.
An oral vaccine against the tumor-stromal antigen FAP (fibroblast activation protein) inhibits growth of chemo-resistant murine colon-carcinoma
Authors: Markus Loeffler, Joerg Krueger, Andreas G. Niethammer, Ralph A. Reisfeld
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

4841 

In an attempt to further broaden the array off currently available targets for the immunotherapy of cancer, we successfully engineered a DNA-based vaccine against a tumor-stromal antigen, fibroblast activation protein (FAP). This cell surface antigen is selectively overexpressed in stromal fibroblasts of various epithelial cancers, such as colon, breast and lung. Generally, normal adult tissues are devoid of any FAP-expression, although it can be found during wound-healing co-expressed with CD26, a T-cell activation antigen with which it shares 48% amino acid sequence identity. In addition, transient expression of FAP in some fetal mesenchymal tissues has been described. This DNA-vaccine, carried by attenuated Salmonella typhimurium , and co-expressing either CD40LT or IL-2 plus CCL21, inhibited the growth of primary s.c. tumors in a prophylactic model as well as the dissemination of pulmonary metastases in a therapeutic model of a multi-drug resistant clone of CT-26 murine colon carcinoma cells. By inducing specific lysis of cells overexpressing FAP with purified, CD8-positive cells from splenocytes of vaccinated mice, we were able to show that this vaccine was indeed capable of breaking peripheral immune tolerance against this self-antigen. Additionally, we found up-regulation of T-cell, NK-cell and dendritic cell activation markers and costimulatory molecules, indicating further involvement of the adoptive immune system. Another very interesting and possibly clinically relevant finding was the fact that immunized mice compared to control mice were able to incorporate more of the low-molecular weight dye fluorescein (Mr 376) as well as the high-molecular weight compound Evans-blue albumin (Mr 68,500) in tumors, thereby opening a venue to combine immuno- and chemotherapies. In summary, this DNA-based vaccine provided protection against growth of primary as well as metastatic multi-drug resistant colon carcinoma cells and is anticipated to significantly ameliorate chemotherapy by improving delivery of therapeutic agents to tumors, a project currently under investigation in our laboratory.
Studies on Lymphocytes. I. Lymphopenia Produced by Prolonged Extracorporeal Irradiation of Circulating Blood
Authors: EUGENE P. CRONKITE, CORNELIUS R. JANSEN, GEORGE C. MATHER, NIELS O. NIELSEN, EDWARD A. USENIK, EMIL R. ADAMIK, CLYDE R. SIPE
Journal: Blood (1962)
Abstract 11605: Proteinase-Activated Receptor-2 is Responsible for Amplified Function of Transient Receptor Potential Channel A1 in Skeletal Muscle Sensory Neurons of Rats With Peripheral Artery Disease
Authors: Jihong Xing, Jian Lu, Jianhua Li
Journal: Circulation (2014)

Background: Limb ischemia occurs in peripheral artery disease (PAD). Sympathetic nerve activity that regulates blood flow directed to the limbs is augmented during exercise in this disease and transient receptor potential channel A1 (TRPA1) in thin-fiber muscle afferents contributes to the amplified sympathetic responses. The objective of this study was to determine the role played by proteinase-activated receptor-2 (PAR2) in regulating abnormal TRPA1 function. Methods: A rat model of femoral artery ligation was employed to study PAD. Dorsal root ganglion (DRG) tissues of control limbs and limbs with 24 hours of femoral occlusion were obtained to examine the protein levels of PAR2 using western blot analysis. Also, current responses induced by activation of TRPA1 in skeletal muscle DRG neurons of control limbs and ligated limbs were characterized using whole-cell patch clamp methods. All data are presented as mean ± SE. Results: Femoral occlusion significantly increased expression of PAR2 in DRG (optical density: 1.06±0.03 in control vs. 1.45±0.04 after occlusion, P&lt; 0.05; n = 6 in each group). In addition, femoral occlusion amplified the amplitude of DRG current responses evoked by stimulation of TRPA1 with AITC (a TRPA1 agonist, 100 μM). The peak amplitude of TRPA1 currents was 0.28±0.03 nA in control and 0.41±0.04 nA ( P&lt; 0.05 vs. control; n = 12 in each group) after occlusion, respectively. Activation of PAR2 with SL-NH2 (a PAR2 agonist, 100 μM) increased the TRPA1 currents by 78±10% in DRG neurons of control limb and by 125±10% in DRG neurons of ligated limb ( P&lt; 0.05 vs. control; n = 8 in each group). Moreover, the potentiating effects of PAR2 activation were significantly inhibited by application of phospholipase C (PLC) inhibitors or phosphatidylinositol-4,5-bisphosphate (PIP2). Conclusions: A functional interaction in PAR2 and TRPA1 in muscle sensory nerves likely contributes to the amplified sympathetic responsiveness observed in PAD and that the PLC/PIP2 is engaged in sensitization mechanism of TRPA1. These findings provide a pathophysiological basis for autonomic responses during exercise activity in this disease, which may further help to aim at a potential therapeutic approach for improvement of blood flow in PAD patients.
Abstract 333: Evaluation of the mixed solution of sodium hyaluronate and hydroxyethylstarch on gynecologic cancer cell line
Authors: Ha-Young Lee, Hyun-Jung Cho, Shin-Wha Lee, Sang-Eun Lee, Dae-Yeon Kim, Jong-Hyeok Kim, Yong-Man Kim, Young-Tak Kim, Joo-Hyun Nam
Journal: Cancer Research (2015)

Abstract Effect of hyaluronic acid and hydroethyl starch mixture in ovarian cancer cell Objective: Post-operative tissue adhesion is a very serious problem in patients with ovarian cancer. This study is to investigate the role of hyaluronic acid and hydroethyl starch mixture against the tissue adhesion through in vitro experimentations with ovarian cancer cell lines. Methods: We used different concentrations of hyaluronic acid and hydroethyl starch (HA/HES) mixture in SKOV3 cell lines. We performed the adhesion and proliferation inhibition assay in different method, mixing and spreading cells. For the migration inhibition assay, we evaluated the effect according to the concentration of HA/HES mixture. The wound-healing assay was performed after artificial injury and physical barrier of 100% HA/HES mixture was evaluated. Results: In adhesion and proliferation inhibition assay, the viable adherent cells were decreased according to the concentration of HA/HES mixture. The confluence increased over time, except for 100% HA/HES mixture. This result was more obvious in spreading method. The wound recovery was slow in high concentration of HA/HES mixture in the migration inhibition assay and wound-healing assay. The physical barrier of 100% HA/HES mixture inhibited the cell growth until 48 hours. Conclusion: The proliferation and recovery inhibition of SKOV3 cell lines using HA/HES mixture was confirmed and the inhibitory effect appeared to be in proportion of the concentration of HA/HES mixture. This growth inhibition effect of HA/HES mixture will be useful clinically in patients with ovarian cancer Citation Format: Ha-Young Lee, Hyun-Jung Cho, Shin-Wha Lee, Sang-Eun Lee, Dae-Yeon Kim, Jong-Hyeok Kim, Yong-Man Kim, Young-Tak Kim, Joo-Hyun Nam. Evaluation of the mixed solution of sodium hyaluronate and hydroxyethylstarch on gynecologic cancer cell line. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 333. doi:10.1158/1538-7445.AM2015-333
Teachers need to know the basics too
Authors: F. Finlay, N. Simpson
Journal: BMJ (1995)

correct dose rapidly, and one can imagine the reaction of parents if children are taken to be weighed before emergency treatment is given.Doses should be stated clearly according to expected body weight by age and should be displayed in accident and emergency departments.Current recommendations for the treatment of anaphylaxis in a 5 year old child are that 0 4 ml of 1/1000 adrenaline should be given by intramuscular injection.2'
P0122 : Type 2 diabetes reduces overall survival and increases the risk of hepatic decompensation in HCV-related liver cirrhosis. Results from a prospective long-term study during 8 years
Authors: E. Vilar-Gomez, L. Calzadilla Bertot, A. Yasells Garcia, Y. Martinez Perez, M. Romero-Gomez, M. Diago
Journal: Journal of Hepatology (2015)
Outbreak of Salmonella enterica serotype Muenster infections associated with goat's cheese, France, March 2008
Authors: D van Cauteren, N Jourdan-da Silva, F  X Weill, L King, A Brisabois, G Delmas, V Vaillant, H de Valk
Journal: Eurosurveillance (2009)

Salmonella enterica serotype Muenster (hereafter referred to as S. Muenster) is rare in France and in Europe. In France, a nationwide outbreak of gastrointestinal illness due to S. Muenster occurred during March and April 2008. Twenty-five laboratory-confirmed cases of S. Muenster were documented by telephone using a trawling questionnaire. Four patients were admitted to hospital and no death was recorded. Among the 21 interviewed cases, 16 reported consumption of goat's cheese in the days prior to symptoms. The investigation incriminated goat's cheese from producer X as being the most likely source of the outbreak. S. Muenster was isolated from both cases and the incriminated goat's cheese. The pulsed-field gel electrophoresis profiles of the food isolates of producer X and the isolates from cases were indistinguishable. Following the withdrawal of the contaminated batch of cheese, the number of cases decreased to its usual level. To our knowledge, this is the first published outbreak of S. Muenster associated with food consumption in Europe.