tbuckley/cabot-search huggingface dataset:
Abstract 2775: The Performance of a New Automated Device for Brachial Artery Flow Mediated Vasodilation Measurement
Authors: Gilles Chironi, Damian Craiem, Janiffer Lacet, Muriel Del-Pino, Jaime Levenson, Alain Simon
Journal: Circulation (2006)

Background: Operator-dependence of most measurement methods of brachial artery flow-mediated vasodilation (FMD) is a limitation for research and clinical applications.  Methods: We developed a new fully automated device for FMD measurement based on robotized manipulation of the probe and computerized analysis of the ultrasound scan. Beat-to-beat diastolic baseline diameter (bD) and hyperemic diameter (hD) (Figure) allowed FMD calculation ((hD-bD)*100/bD). Hyperemic shear rate (hSR) was calculated as 4V/bD, V being the mean centerline blood velocity during the 15 first seconds of reactive hyperaemia. One scan of each subject was read twice by 2 observers in 26 subjects (within reading variability), and 2 scans per subject were measured by the same operator 1 hour apart in 21 subjects (within subject variability).  Results: Coefficients of variation (CV) and standard deviations (SD) of within reading and within subject FMD, bD and hSR are shown in Table. Correlations existed between repeated readings and repeated measurements 1 hour apart for FMD (p  Conclusion: This automated device provides FMD variability of about  1 / 4  that obtained with conventional manual methods. However, within patient FMD variability remains high, because of shear rate variations between measurements.
Clinical Comparison of Incidences, Risk Factors and Outocmes of Chronic Graft-Versus-Host Desease in Unrelated Cord Blood Transplantation and Unrelated Bone Marrow Transplantation
Authors: Yuki Asano-Mori, Atsushi Wake, Kosei Kageyama, Daisuke Kaji, Kazuya Ishiwata, Shinsuke Takagi, Hisashi Yamamoto, Go Yamamoto, Naoyuki Uchida, Koji Izutsu, Akiko Yoneyama, Shigeyoshi Makino, Shuichi Taniguchi
Journal: Blood (2014)
Abstract 442: Flow-Dependent Regulation of Angiopoietin-2
Authors: Winfried Goettsch, Corina Gryczka, Thomas Korff, Evelyn Ernst, Claudia Goettsch, Jochen Seebach, Hans J Schnittler, Hellmut G Augustin, Henning Morawietz
Journal: Circulation (2007)

Background: Endothelial cells are constantly exposed to high or low shear stress in arteries and veins by the flowing blood. Angiopoietin-2 (Ang-2) is acting as a critical regulator of vessel maturation and endothelial cell quiescence. In this study, we determined the effect of low and high laminar shear stress on the expression and release of angiopoietin (Ang-)2 in human endothelial cells, studied the role of nitric oxide and protein kinases in this context, determined the impact of VEGF on Ang-2, studied the expression, activity and translocation of the forkhead box O transcription factor FOXO1 by low and high shear stress, and analyzed the vessel- and flow-dependent expression of Ang-2 in vivo . Methods and Results: Primary cultures of human umbilical vein endothelial cells (HUVEC) were subjected to laminar shear stress at different physiological levels of laminar shear stress of 1, 5, 10, 15, and 30 dyne/cm 2 in a cone-and-plate viscometer. Ang-2 mRNA, protein expression and release was upregulated by 24 h of low (1 dyne/cm 2 ), but downregulated by high flow (30 dyne/cm 2 ) in human endothelial cells. Increased endothelial NO synthase expression and NO formation was not affecting regulation of Ang-2 by low or high flow. Tie2 protein expression, but not Tie2 phosphorylation was induced by high flow. Furthermore, low and high flow increased VEGF-A expression. Inhibition of VEGFR-2 prevented upregulation of Ang-2 by low flow, but not downregulation of Ang-2 by high flow. Upregulation of Ang-2 by VEGF was reduced by application of high flow. Forkhead box O (FOXO) transcription factor FOXO1 has been shown to regulate Ang-2 expression in endothelial cells. FOXO1 binding activity was reduced by high flow. Nuclear localization of transcription factor FOXO1 was not changed by low flow, but reduced by high flow. In vivo , Ang-2 was higher expressed in veins compared to arteries. Arterial ligation augmented Ang-2 expression in distal arterial low flow areas. Conclusion: Our results support a VEGF-dependent induction of Ang-2 in low flow areas, and FOXO1-dependent downregulation of Ang-2 in high flow areas. These data suggest a new mechanism of flow-dependent regulation of vessel stability and differentiation.
Association of D222G substitution in haemagglutinin of 2009 pandemic influenza A (H1N1) with severe disease
Authors: G C Mak, K W Au, L S Tai, K C Chuang, K C Cheng, T C Shiu, W Lim
Journal: Eurosurveillance (2010)

Preview this article: Association of D222G substitution in haemagglutinin of 2009 pandemic influenza A (H1N1) with severe disease, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/15/14/art19534-en-1.gif
Abstract 2936: Intraoperative Optimization of Cardiac Resynchronization Therapy using Intracardiac Echocardiography can maximize benefits in patients with Refractory Heart Failure
Authors: Sanjeev Saksena, Praveen Dala, Mohamed Ahmed, Philip Mathew, Lyndon Akers, Mary A Viggiano
Journal: Circulation (2006)

Background: Cardiac resynchronization therapy (CRT) is used for refractory heart failure (HF) but its benefit has been unpredictable. Intraoperative programming of rate, atrioventricular(AV) or int...
Key Results of International Randomized Open-Label Clinical Study of BCD-020 (rituximab biosimilar candidate) in Patients with B-Cell Non-Hodgkin’s Lymphoma
Authors: Kamil Kaplanov, Andrey Zaritskiy, Sergey Alexeev, Elena Volodicheva, Alexander Loginov, Rashida Orlova, Victoria Dvornichenko, Marina Kosinova, Olga Serduk, Vladimir Milovanov, Alexander Myasnikov, Shekar Patil, Shekar Patil, Bharath Rangarajan, Senthil Jagannathan Rajappa, Minish Jain, Sharanabasappa Nirni, Akhil Deka, Grigoriy B Rekhtman, Iryna Kryachok, Zvenyslava Maslyak, Ekaterina Chernyaeva, Roman Ivanov, Alexander Isaev
Journal: Blood (2014)
Abstract P292: Severe Obesity is Associated with Dramatic Increase in Cardiovascular Disease Risk Factor Prevalence: Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Robert Kaplan, Larissa M Avilés-Santa, Christina M Parrinello, Sheila Castañeda, Arlene L Hankinson, Carmen R Isasi, Orit Birnbaum-Weitzman, Ryung Kim, Martha L Daviglus, Gregory A Talavera, Neil Schneiderman, Jianwen Cai
Journal: Circulation (2013)

Introduction: Prevalence of severe obesity is increasing, especially among the young Hispanic population. Methods: In the HCHS/SOL cohort of 18-74 year old US Hispanics, we examined gradients across BMI and age in CVD risk factors. Results: Approximately one in five males (total N = 6,547) and one in ten females (total N=9,797) met criteria for class II obesity (BMI 35 - 40 kg/m 2 ) or class III obesity (BMI ≥ 40 kg/m 2 ). The prevalence of hypertension, diabetes, and elevated C-reactive protein rose with each successive class of overweight/obesity. In contrast, the prevalence of elevated levels of total cholesterol, LDL-c and triglycerides increased across normal weight, overweight (BMI 25 - 30 kg/m 2 ), and class I obese (BMI 30 - 35 kg/m 2 ) groups, but did not increase in frequency across class I, class II, and class III obesity groups. The Figure depicts isolines that identify age- specific subgroups of the normal-weight and class II - III obese groups that had the same estimated prevalence of CVD risk factors, with 95 percent confidence intervals. Among young adults with class II or III obesity, the prevalence of hypertension, diabetes, and the combination of three or more CVD risk factors was similar to that among normal-weight individuals (BMI 18.5 - 25 kg/m 2 ) who were 15 to 30 years older. Among young obese individuals, the prevalence of low HDL-c levels and high C-reactive protein levels exceeded that among the oldest adults in the cohort. CVD risk factors had stronger, more consistent gradients across the BMI categories among men than among women. Conclusion: Class II and III obesity, defined as BMI ≥ 35 kg/m 2 , are common in the Hispanic/Latino population. Young adults with these severe forms of obesity have dramatically increased frequency of cardiometabolic risk factors. The age-related accumulation of multiple CVD risk factors, such as is typically seen in normal-weight individuals, is accelerated by 1-2 decades in severly overweight women and by 2-3 decades in severely overweight men.
Abstract 4626: Optimal Dose of Adv-hHCN4 Creates Stable and Long-lasting Biopacing Activity in Cultured Ventricular Cardiomyocytes
Authors: Yong-Fu Xiao, Alena Nikolskaya, Lepeng Zeng, Xiaohong Qiu, Deborah A. Jaye, Vinod Sharma, Daniel C. Sigg
Journal: Circulation (2008)

Purpose: Hyperpolarization-activated cyclic nucleotide-gated (HCN) genes have been successfully used as a strategy for recreating cardiac biological pacemakers in animal models. However, optimal dose of HCN and toxicity from HCN overexpression have not been investigated. Therefore, we assessed the effects of various titers of adenoviral human HCN4-GFP vector (Adv-hHCN4) on cardiomyocytes. Methods: Neonatal rat ventricular myocytes (NRVMs) were isolated, selected and cultured on microelectrode arrays to assess their automaticities. Morphology and apoptosis with and without HCN or Ca 2+ channel inhibitor were also assessed. Results: Beating rates significantly increased in NRVMs after hHCN4 infection (Fig. 1 ). For example, the rates were gradually increased to 235±11 beat/min on day 7 after hHCN4 infection with 1×10 5 PFU/array. In contrast, control cells showed low rates. NRVMs with ≥10 6 PFU/array Adv-hHCN4 reached faster rates early and subsequently stopped beating (Fig. 1 ). In addition, myocytes with ≥10 6 PFU/array Adv-hHCN4 underwent significant apoptosis (&gt;50%) which potentially resulted from hHCN4 overexpression and was blocked by the HCN channel blocker Cs + (1 mM), but not by the Ca 2+ channel inhibitor nifedipine. In addition, myocytes infected with ≥10 6 PFU/array Adv-GFP maintained normal morphology and rate. Our data demonstrate that hHCN4 transfer significantly and dose-dependently increased beating rates of NRVMs. However, overexpression of HCN could cause apoptosis. Therefore, an optimal dose of HCN gene is important for reducing toxicity and creating stable and long-lasting biopacing activity in cardiomyocytes in vitro, and probably also in vivo. Figure 1. Effects of hHCN4 infection on automaticities of neonatal rat ventricular myocytes. Each data point represents an averaged beating rate (mean ± SE) from 8 to 10 arrays. Various titers (1×10 5 to 1×10 7 PFU/500,000 cells per array) of Adv-Hhcn4 (expect control) were added to the arrays after measurements on day 0 (see the arrow)
“One stop” approach may help prevent cervical cancer
Authors: Susan Mayor
Journal: BMJ (2003)

Treating women for potentially precancerous cervical lesions the same day they are detected could offer a practical approach to preventing cervical cancer in some developing countries, a study in Thailand has shown.

A group of 12 specially trained nurses offered women in four districts in Roi Et province—a mainly rural area—screening for cervical cancer using visual inspection of the cervix with acetic acid wash. Those who tested positive (showing raised and thickened white plaques) were offered cryotherapy during the same visit, after counselling about the benefits, potential risks, and probable side effects.

Results showed that 13% of the 5999 women who were screened during the seven month study tested positive. Nearly all (99%) of the women who were considered eligible accepted immediate treatment with cryotherapy. Eligibility criteria for treatment included the abnormalities not being suspicious for cancer, not extending on to the vaginal wall, occupying less than 75% of the cervix, and extending less than 2 mm beyond the cryotherapy probe. Oral non-narcotic analgesics were offered to women with bothersome cramping during treatment.

No major complications with treatment were recorded, with only 4% of women treated returning with a perceived problem and 2% needing clinical management other than reassurance about side effects. Follow up data showed no clinically apparent pelvic inflammatory disease or stenosis as a result of cryotherapy (Lancet 2003;361: 814-20) .
Characterisation of aurora kinase inhibitors derived from fragment based lead discovery
Authors: Neil Gallagher, John Lyons, Jayne Curry, Matthias Reule, Valerio Berdini, Dominic Tisi, Lynsey Fazal, Steven Howard, Paul Wyatt, Adrian Gill
Journal: Cancer Research (2006)

4915   The protein kinases Aurora A and B have been associated with the incidence and severity of several cancers. As a consequence they have been the focus of a significant amount of drug discovery activity. We describe here a series of Aurora A and B inhibitors that have been developed using a fragment based lead discovery approach which couples high throughput x-ray crystallography of the target protein with fragment soaks from the Astex fragment library. The Aurora kinases regulate mitosis and are only expressed in cells that are actively dividing, making them ideal targets for therapeutic intervention. Inhibition of Aurora-B induces a polyploid phenotype, via abnormal cytokinesis in cells progressing through mitosis and results ultimately in apoptosis. We have profiled a series of compounds for anti-tumour activity in in-vitro kinase assays, in cells and in animals. We tested a number of compounds from the series in a number of leukemic cell lines and showed sensitivity in each case to the Aurora inhibitor. We also tested the therapeutic window for the compound by comparing the cell cycle effects in tumour lines to normal mammary epithelial cells. Following successful profiling of the series in DMPK experiments we also wanted to show how PD effects might translate to efficacy in animal models. Thus, we analysed xenograft tumours using single doses of active compound shown to be efficacious in-vivo for inhibition of surrogate markers. The markers tested included phosphorylation on serine 10 of histone H3, a known Aurora substrate after single doses and p53 stabilisation in tumour xenografts after multiple doses of active compound using IHC as well as the polyploidy phenotype in the tumour sections from later timepoints post dosing. The activity of our series has been tested in a number of different human tumour xenograft models. We anticipate initiation of clinical development for a compound from this series in the near future.
CpG island methylation of CHFR does not cause chromosomal instability in colorectal cancer
Authors: Keigo Kimura
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

4986 

Colorectal cancer (CRC) can progress through pathways either of chromosomal instability (CIN) or microsatellite instability (MSI). While MSI is caused by mismatch repair defects, responsible mechanism (gene) for CIN is not fully understood. Since CIN cells fail to undergo mitotic arrest following spindle damage, mutations in spindle checkpoint genes may account for CIN. However, mutations identified in spindle checkpoint genes are rare in human cancers. The CHFR gene, which was cloned by Scolnick and Halazonetis in search for a novel mitotic checkpoint gene having fork-head association motifs, has been suggested to play a key role in the mitotic prophase checkpoint. Recent study showed that promoter CpG islands of Chfr were methylated in 37% of the primary CRCs and in 10% of primary non-small cell lung carcinomas. The aim of this study is to examine hypermethylation of the Chfr in CRC show any association with CIN phenotype. The CIN was identified by loss of heterozygosity (LOH) in chromosomal arms 1p, 2p, 5q, 17p, and 18q, as well as by subtraction of microsatellite instability phenotype. We found Chfr CpG island methylation in 49 (38.0%) of 129 primary CRCs. Among the 129 CRCs examined 68 (52.7%) showed LOH in at least one chromosome examined. Among the 68 CRCs with LOH, 25(36.8%) showed promoter methylation in Chfr, while 24 (39.3%) showed promoter methylation in 61cancers without LOH examined. We also found that there was no relation between CpG island methylation of Chfr and MSI phenotype. Our data suggest that although frequency of CpG island methylation in Chfr is high, there was no association in promoter methylation of Chfr with either LOH or MSI.
Abstract 15364: Cardiac Magnetic Resonance T1 Mapping Pre and Post Contrast Characterizes the Myocardium in Orthotopic Heart Transplantation Recipients without Active Rejection
Authors: Patrizia Pedrotti, Angela Milazzo, Giuseppina Quattrocchi, Franco Zanotti, Valentina Guida, Maria Frigerio, Alberto Roghi, Ornella Rimoldi
Journal: Circulation (2012)
Intravitreal Aflibercept for Diabetic Macular Edema
Authors: David M. Brown, Ursula Schmidt-Erfurth, Diana V. Do, Frank G. Holz, David S. Boyer, Edoardo Midena, Jeffrey S. Heier, Hiroko Terasaki, Peter K. Kaiser, Dennis M. Marcus, Quan D. Nguyen, Glenn J. Jaffe, Jason S. Slakter, Christian Simader, Yuhwen Soo, Thomas Schmelter, George D. Yancopoulos, Neil Stahl, Robert Vitti, Alyson J. Berliner, Oliver Zeitz, Carola Metzig, Jean-François Korobelnik
Journal: Ophthalmology (2015)
Abstract 19998: Coronary Artery Calcium and Bone Mineral Density Measured Computed Tomography: Impact of Age, Gender and Ethnicity
Authors: Naser Ahmadi, Song S Mao, Fereshteh Hajsadeghi, Ben Arnold, Sarkis Kiramijyan, Yanlin Gao, Ferdinand Flores, Matthew Budoff
Journal: Circulation (2010)
Abstract A85: Collagen triple helix repeat containing-1 enhances the aggressiveness of pancreatic tumor by increased cancer cell motility and adhesiveness
Authors: Leem Sun-Hee, Kang Tae-Hong, Chung Jin Woong, Hwang Yeonsil, Kim Seokho, Koh Sang Seok
Journal: Cancer Research (2015)

Abstract Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein involved in vascular remodeling, bone formation and developmental morphogenesis. CTHRC1 is expressed in human cancers such as breast cancer and melanoma. In this study, we show that CTHRC1 is highly expressed in human pancreatic cancer tissues and plays a role in the progression and metastasis of the disease. CTHRC1 promoted primary tumor growth and metastatic spread of cancer cells to distant organs in orthotopic xenograft tumor mouse models. Overexpression of CTHRC1 in cancer cells resulted in increased motility and adhesiveness. CTHRC1 activated several key signaling molecules, including Src, focal adhesion kinase, paxillin, mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase and Rac1. Treatment of xenograft mice of pancreatic cancer cells with a CTHRC1-specific monoclonal antibody led to significantly smaller tumor sizes compared with those of untreated control mice. Collectively, our results suggest that CTHRC1 has a role in pancreatic cancer progression and metastasis by regulating migration and adhesion activities of cancer cells. Citation Format: Leem Sun-Hee, Kang Tae-Hong, Chung Jin Woong, Hwang Yeonsil, Kim Seokho, Koh Sang Seok. Collagen triple helix repeat containing-1 enhances the aggressiveness of pancreatic tumor by increased cancer cell motility and adhesiveness. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A85.
Abstract 3380: Heart Failure Reversal by Ventricular Unloading in Patients With Chronic Cardiomyopathy: Criteria for Weaning From Ventricular Assist Devices
Authors: Michael Dandel, Yuguo Weng, Henryk Siniawski, Hans B Lehmkuhl, Evgenij Potapov, Thomas Krabatsch, Christoph Knosalla, Roland Hetzer
Journal: Circulation (2009)
Abstract 3446: Therapeutic Neovascularization by Catheter-Based, Intramyocardial Gene Transfer of Naked DNA Encoding Human Placental Growth Factor in Swine Chronic Myocardial Ischemia
Authors: Atsuhiko Kawamoto, Hiroto Iwasaki, Hideki Iwaguro, Atsushi Nakahira, Akira Oyamada, Hiroshi Akimaru, Peter Carmeliet, Takayuki Asahara
Journal: Circulation (2008)

Background: We have reported that intramyocardial transfer of plasmid encoding human placental growth factor (phPlGF) augments myocardial angiogenesis, inhibits myocardial apoptosis and left ventri...
Role of plasma membrane fluidity alterations in tumor cell sensitization to apoptosis-inducing stimuli: Therapeutic implications
Authors: Stravoula Baritaki, Peggy Kanellou, Stavros Apostolakis, Demetrious A. Spandidos, Benjamin Bonavida
Journal: Cancer Research (2006)

1262  Alterations in membrane fluidity can seriously affect functional properties of the cell and may cause the induction of apoptotic pathways resulting in cell death. The molecular signaling pathways leading to apoptosis are promising areas of research investigation for the underlying molecular mechanisms involved in tumor cell resistance to drug/immune mediated apoptosis and the development of new therapeutic compounds. Recent findings indicate that anti-cancer agents induce apoptosis, directly or indirectly, through alterations of tumor cell membrane fluidity. Also, changes in membrane fluidity resulted in aggregation of death receptors (eg Fas, DR4, DR5) and activation of the apoptotic stimulus. The objective of this study was to investigate the relationship of tumor cell membrane fluidity alterations and cell sensitivity to apoptosis-inducing stimuli. We hypothesized that the resistant phenotype of the tumor cells is, in large part, regulated by the fluidity of the tumor cell membranes. This hypothesis was tested in an vitro tumor cell model system. We selected the drug and immune-resistant prostate tumor cell line, PC-3, for this study. Initially we treated PC-3 cells with lipofectamine for transfection and we observed that there was significant spontaneous induction of apoptosis compared to tumor cells treated with medium alone. Apoptosis was measured by activation of the effector caspase-3. These studies suggested that lipofectamine may also sensitize the tumor cells to drug and immune mediated apoptosis. Hense, treatment of PC-3 cells with lipofectamine for 6 h and wash, followed by treatment with CDDP or vincristine for 18 h resulted in significant apoptosis compared to treatment with the drugs alone. Likewise, lilofectamime treated PC-3 cells with TRAIL resulted in significant potentiation of apoptosis compared to treatment with TRAIL alone. These findings corroborate the above hypothesis and suggest that tumor cell-resistance can be modified by alterations of the membrane lipid composition. The mechanism by which alterations of membrane fluidity is responsible for changes in resistance is not clear. We propose that alteration in membrane fluidity may result in alterations in lipid raft composition and alteration of survivor signaling apoptotic pathways and aggregation of death receptors. In support of this hypothesis, recent studies have demonstrated that treatment of tumor cells with CDDP resulted in redistribution of the death receptor Fas into lipid rafts (Lacour S., et al., Cancer Research 64: 3593-3598, 2004). In conclusion, these studies suggest that alterations of lipid composition of tumor cells may be a therapeutic option, in combination with conventional therapeutics, in the treatment of resistant tumor cells.