tbuckley/cabot-search huggingface dataset:
Ultrasound-Guided Strategy for Provisional Stenting With Focal Balloon Combination Catheter
Authors: Axel W. Frey, John M. Hodgson, Christian Müller, Hans-Peter Bestehorn, Helmut Roskamm
Journal: Circulation (2000)

Background —Intracoronary ultrasound (ICUS) has provided insights into vascular pathology and interventional therapy. The Strategy for ICUS-Guided PTCA and Stenting (SIPS) trial tested the hypothesis that routine ICUS guidance of coronary interventions improves outcome. Methods and Results —A single-center consecutive-patient randomized design (with 6-month angiographic and 2-year clinical follow-up) was used. Consecutive patients (no chronic total occlusions or emergency procedures) were randomized to ICUS-guided provisional stenting or standard angiographic guidance. Quantitative angiographic minimal lumen diameter (MLD), angiographic restenosis, clinically driven target lesion revascularization, and major adverse cardiac events (MACEs) were evaluated. A total of 291 procedures (356 lesions) were included. Procedure success was higher in the ICUS-guided group than the group randomized to standard guidance (94.7% versus 87.4%, respectively; P =0.033), whereas time (65.2±31.0 versus 60.5±34.0 minutes, P =0.18) and contrast use (209.3±94.1 versus 197.5±89.5 mL, P =0.23) were not significantly different. Stenting rates were similar (49.7% versus 49.5%, P =0.89). Acute gain was greater in the ICUS-guided group than in the standard guidance group (1.85±0.72 versus 1.67±0.76 mm, respectively; P =0.02). Angiographic 6-month analysis revealed no difference in MLD (1.71±0.94 versus 1.57±0.90, P =0.19) or binary restenosis rate (&gt;50% diameter stenosis) (29% versus 35%, P =0.42). Clinical follow-up (602±307 days) showed a significant decrease in clinically driven target lesion revascularization in the ICUS group compared with the standard guidance group (17% versus 29%, respectively; P =0.02). Conclusions —Although angiographic MLD did not differ significantly after 6 months, ICUS-guided provisional stenting improved 2-year clinical results after intervention.
Bicuspid aortic valve in competitive athletes
Authors: L Stefani, G Galanti, L Toncelli, P Manetti, M C Vono, M Rizzo, N Maffulli
Journal: British Journal of Sports Medicine (2007)

Aim: Bicuspid aortic valve (BAV) is a common congenital cardiac condition. The presence of BAV in non-elite athletes has been poorly investigated; it is usually asymptomatic until valvular stenosis, regurgitation or other vascular alterations are evident. Design: Over a three-year period, 2273 competitive athletes were consecutively investigated with transthoracic echocardiography. The traditional parameters, the aortic root dimensions at four levels and the systolic and diastolic flow of aortic valve, were studied with continuous Doppler according to the echo guidelines. Setting: The study protocol included all the non-elite athletes investigated for the first evaluation to obtain eligibility. Patients: 2273 competitive athletes aged 8–60 years from several sports and regularly trained were evaluated with anamnesis, clinical check-up and echocardiography in order to exclude subjects with systemic or congenital heart disease. Results: BAV was diagnosed in 58 athletes (2.5%). Of these, nine had normal valvular function, 47 had abnormal valvular function with mild–moderate aortic regurgitation, and two had moderate stenosis. Aortic root dimensions at all levels were significantly greater in athletes with BAV than in athletes with a normal tricuspid valve. No relation was found with age, body surface area, aortic regurgitation or years of training. Conclusions: BAV is a relatively common congenital cardiac disease in athletes and commonly asymptomatic for a long time. This study suggests the usefulness of evaluating young athletes using echocardiography at least once when they start their sporting activity.
Parathyroid hormone improves contractile performance of adult rat ventricular cardiomyocytes at low concentrations in a non-acute way
Authors: I. Tastan, R. Schreckenberg, S. Mufti, Y. Abdallah, H. M. Piper, K.-D. Schluter
Journal: Cardiovascular Research (2009)

In patients with congestive heart failure, plasma parathyroid hormone (PTH) levels are positively associated with cardiac function. PTH, used to mobilize stem cells from the bone marrow after myocardial infarction, causes an increased left ventricular ejection fraction. The aim of this study was to investigate whether low but plasma-relevant concentrations of PTH directly influence the contractile properties of cardiomyocytes.Isolated adult rat ventricular cardiomyocytes were exposed to PTH(1-34) or full-length PTH at picomolar concentrations for 24 h. Cell shortening was measured at 2 Hz as a cellular correlate of inotropic responsiveness. Intracellular calcium was measured in Fura-AM-loaded cells. PTH(1-3) (20-200 pM) and full-length PTH (200 pM) increased cell shortening within 24 h. PTH had no effect on cell size, but resting and peak systolic calcium concentrations were elevated. The beneficial effect of PTH was mediated via its cAMP/protein kinase A-activating domain and attenuated by addition of a protein kinase A inhibitor. In contrast, PTH peptides representing a protein kinase C-activating domain but not a cAMP/protein kinase A-activating domain or peptides that represent none of these domains had no effect on cell shortening. The effect of PTH on cell shortening was strong at low concentrations of extracellular calcium but declined at higher calcium concentrations. PTH downregulated the expression of the calcium sensing receptor, a receptor known to antagonize the action of PTH on calcium transport. Furthermore, PTH antagonized the angiotensin II-induced loss of cell function.Low concentrations of PTH improve cell shortening by increasing calcium load at rest. By this mechanism cardiomyocytes compensate reduced extracellular calcium levels as they occur in patients with heart failure.
High Glucose Blunts Vascular Endothelial Growth Factor Response to Hypoxia via the Oxidative Stress-Regulated Hypoxia-Inducible Factor/Hypoxia-Responsible Element Pathway
Authors: Pisut Katavetin, Toshio Miyata, Reiko Inagi, Tetsuhiro Tanaka, Ryoji Sassa, Julie R. Ingelfinger, Toshiro Fujita, Masaomi Nangaku
Journal: Journal of the American Society of Nephrology (2006)

Vascular endothelial growth factor (VEGF) is an important survival factor for endothelial cells in hypoxic environments. High glucose regulates certain aspects of VEGF expression in various cell types, including proximal tubular cells. Thus, ambient glucose levels may modulate the progression of chronic kidney disease, especially diabetic nephropathy. Immortalized rat proximal tubular cells (IRPTC) were cultured for 24 h under hypoxic conditions (1% O(2)), with or without high d-glucose (25 mM), or with or without high l-glucose (25 mM). Controls included culture in normoxic conditions and normal d-glucose (5.5 mM). VEGF mRNA expression was assessed by real-time quantitative PCR, and VEGF protein in the supernatant was assessed by ELISA. Hypoxia increased VEGF expression. This response was significantly blunted by high d-glucose (1.98 +/- 0.11- versus 2.65 +/- 0.27-fold increase for VEGF mRNA expression, 252.8 +/- 14.7 versus 324.0 +/- 11.5 pg/10(5) cells for VEGF protein; P < 0.05 both) but not by high l-glucose. It is interesting that hydrogen peroxide also blunted this response, whereas alpha-tocopherol restored the VEGF response to hypoxia in the presence of high d-glucose. For determination of involvement of the hypoxia-inducible factor (HIF)/hypoxia-responsible element (HRE) pathway, IRPTC that were stably transfected with HRE-luciferase were cultured under the previous conditions. High d-glucose also reduced luciferase activity under hypoxia, whereas alpha-tocopherol restored activity. In vivo experiments using streptozotocin-induced diabetic rats confirmed that hyperglycemia blunted HIF-HRE pathway activation. Insulin treatment restored activation of the HIF-HRE pathway in streptozotocin-induced diabetic rats. In conclusion, high glucose blunts VEGF response to hypoxia in IRPTC. This effect is mediated by the oxidative stress-regulated HIF-HRE pathway.
Requirement for Tyrosine Residues 315 and 319 within ζ Chain–Associated Protein 70 for T Cell Development
Authors: Qian Gong, Xiaohua Jin, Antonina M. Akk, Niko Foger, Mike White, Guoqing Gong, Julie Bubeck Wardenburg, Andrew C. Chan
Journal: The Journal of Experimental Medicine (2001)

Engagement of the T cell antigen receptor (TCR) induces the transphosphorylation of the ζ chain–associated protein of 70,000 Mr (ZAP-70) protein tyrosine kinase (PTK) by the CD4/8 coreceptor associated Lck PTK. Phosphorylation of Tyr 493 within ZAP-70's activation loop results in the enzymatic activation of ZAP-70. Additional tyrosines (Tyrs) within ZAP-70 are phosphorylated that play both positive and negative regulatory roles in TCR function. Phosphorylation of Tyr residues (Tyrs 315 and 319) within the Interdomain B region of the ZAP-70 PTK plays important roles in the generation of second messengers after TCR engagement. Here, we demonstrate that phosphorylation of these two Tyr residues also play important roles in mediating the positive and negative selection of T cells in the thymus.
Active and passive smoking in relation to lung cancer incidence in the Women's Health Initiative Observational Study prospective cohort
Authors: A. Wang, J. Kubo, J. Luo, M. Desai, H. Hedlin, M. Henderson, R. Chlebowski, H. Tindle, C. Chen, S. Gomez, J.E. Manson, A.G. Schwartz, J. Wactawski-Wende, M. Cote, M.I. Patel, M.L. Stefanick, H.A. Wakelee
Journal: Annals of Oncology (2014)
Uptake, yield of neoplasia, and adverse effects of flexible sigmoidoscopy screening
Authors: W S Atkin, A Hart, R Edwards, P McIntyre, R Aubrey, J Wardle, S Sutton, J Cuzick, J M A Northover
Journal: Gut (1998)

<i>Background</i>—A multicentre randomised controlled trial to evaluate screening by "once only" flexible sigmoidoscopy (FS) for prevention of bowel cancer is in progress. <i>Aims</i>—To pilot the trial protocol examining rates of attendance, yield of neoplasia, and adverse effects. <i>Subjects</i>—A total of 3540 subjects aged 55–64 years in Welwyn Garden City (WGC) and 19 706 in Leicester (LE). <i>Methods</i>—Subjects responding positively to an "interest in screening" questionnaire were randomised to invitation for screening or control arms. Small polyps were removed during screening. Colonoscopy was undertaken for high risk polyps (more than two adenomas, size at least 1 cm, villous histology, severe dysplasia, or malignancy). The remainder were discharged. <i>Results</i>—In WGC and LE respectively, 59% and 61% indicated an interest in screening, of which 74% and 75% attended. Adenomas were detected in 10% and 9%, respectively, and cancers in 7 per 1000 (in both centres), 55% at Dukes's stage A. The colonoscopy referral rate was 6% in both centres. Mild, short lived bleeding occurred in 3%. One person died following surgery. <i>Conclusions</i>—Compliance rates, yield of adenomas, and referral rate for colonoscopy were as expected, but cancer detection rates were higher. Adverse effects following sigmoidoscopy or colonoscopy were mild and transient, but there was one postoperative death. A randomised trial is necessary to evaluate fully the risks and benefits of this intervention.
An Open-Label, Phase I Study of the Polo-like Kinase-1 Inhibitor, BI 2536, in Patients with Advanced Solid Tumors
Authors: Ralf-Dieter Hofheinz, Salah-Eddin Al-Batran, Andreas Hochhaus, Elke Jäger, Volker L. Reichardt, Holger Fritsch, Dirk Trommeshauser, Gerd Munzert
Journal: Clinical Cancer Research (2010)

This phase I, open-label, dose-escalation study investigated the maximum tolerated dose (MTD) of BI 2536, a small-molecule polo-like kinase (Plk)-1 inhibitor, in two treatment schedules in patients with advanced solid tumors. Secondary objectives included evaluation of safety, efficacy, and pharmacokinetics.Patients received a single i.v. dose of BI 2536 as a 1-hour infusion on days 1 and 8 or a single 24-hour infusion on day 1 of each 21-day treatment course. MTD determination was based on dose-limiting toxicities.Forty-four and 26 patients received each treatment schedule, respectively. The MTD of BI 2536 in the day 1 and 8 schedule was 100 mg per administration (200 mg per course). The MTD for the second dosing schedule was not determined; a 225-mg dose was well tolerated. The most frequently reported treatment-related nonhematologic adverse events were gastrointestinal events and fatigue. Hematotoxicity as the most relevant side effect was similar in both schedules; neutropenia grades 3 and 4 were observed in 16 patients (36.4%) of the day 1 and 8 schedule and 13 patients (50%) of the 24-hour infusion. Fourteen patients (32%) treated in the day 1 and 8 dosing schedule had a best overall response of stable disease. Plasma concentrations of BI 2536 increased dose proportionally, with no relevant accumulation of exposure in the day 1 and 8 dosing schedule. The average terminal half-life was 50 hours.BI 2536 administered in either treatment schedule has adequate safety in patients with advanced solid tumors, warranting further clinical investigation of polo-like kinase-1 inhibitors.
The PPARγ Agonist Pioglitazone Ameliorates Aging-Related Progressive Renal Injury
Authors: Hai-Chun Yang, Sebastien Deleuze, Yiqin Zuo, Sebastian A. Potthoff, Li-Jun Ma, Agnes B. Fogo
Journal: Journal of the American Society of Nephrology (2009)

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against nondiabetic chronic kidney disease in experimental models. Here, we found that the PPAR-gamma agonist pioglitazone protected against renal injury in aging; it reduced proteinuria, improved GFR, decreased sclerosis, and alleviated cell senescence. Increased local expression of PPAR-gamma paralleled these changes. Underlying mechanisms included increased expression of klotho, decreased systemic and renal oxidative stress, and decreased mitochondrial injury. Pioglitazone also regulated p66(Shc) phosphorylation, which integrates many signaling pathways that affect mitochondrial function and longevity, by reducing protein kinase C-beta. These results suggest that PPAR-gamma agonists may benefit aging-related renal injury by improving mitochondrial function.
Smoking, acute mountain sickness and altitude acclimatisation: a cohort study
Authors: Tian-Yi Wu, Shou-Quan Ding, Jin-Liang Liu, Jian-Hou Jia, Zuo-Chun Chai, Rui-Chen Dai, Ji-Zhui Zhao, Qi De Tang, Bengt Kayser
Journal: Thorax (2012)

<h3>Rationale</h3> The relationship between cigarette smoking and acute mountain sickness (AMS) is not clear. <h3>Objective</h3> To assess AMS risk and altitude acclimatisation in relation to smoking. <h3>Methods</h3> 200 healthy non-smokers and 182 cigarette smokers were recruited from Han lowland workers. These were men without prior altitude exposure, matched for age, health status and occupation, who were transported to an altitude of 4525 masl. <h3>Measurements</h3> AMS, smoking habits, arterial saturation (SpO<sub>2</sub>), haemoglobin (Hb), lung function and mean pulmonary artery pressure (PAPm) were assessed upon arrival and after 3 and 6 months. <h3>Main results</h3> Compared with non-smokers, smokers had a lower incidence of AMS and lower AMS scores than non-smokers upon arrival; higher Hb and PAPm associated with lower SpO<sub>2</sub> at 3 and 6 months at altitude; and lower forced expiratory volume in 1 s and maximal voluntary ventilation at 3 and 6 months. <h3>Conclusions</h3> Smoking slightly decreases the risk of AMS but impairs long-term altitude acclimatisation and lung function during a prolonged stay at high altitude.
Abstract 16388: Comparison of Extracorporeal Cardiopulmonary Resuscitation with Conventional Cardiopulmonary Resuscitation in Patients with In-Hospital Cardiac Arrest: A Propensity Score Analysis
Authors: Jin-Ho Choi, Tae Gun Shin, Ik Joon Jo, Min Seob Sim, Hyoung Gon Song, Yeon Kwon Jeong, Yong-Bien Song, Joo-Yong Hahn, Seung Hyuk Choi, Hyeon-Cheol Gwon, Eun-Seok Jeon, Kiick Sung, Wook Sung Kim, Young Tak Lee
Journal: Circulation (2010)

Introduction: Whether the survival of in-hospital cardiac arrest victims could be extended by extracorporeal cardiopulmonary resuscitation (E-CPR) supported with extracorporeal membrane oxygenation...
Trends in world population: how will the millenium compare with the past?
Authors: V. Raleigh
Journal: Human Reproduction Update (1999)

This paper reviews historical and projected trends in world population numbers, and the underlying determinants of those trends. Whereas the world's population has shown little change over most of its one million-year history, the past 200 years have witnessed dramatic changes in fertility, mortality and population growth rates. Recent decades, in particular, have seen unprecedented demographic events, with more people added to the world's population in the past 50 years than in the preceding million. The demographic impact of HIV/AIDS, selective as it is to young adults and infants, is also unprecedented, with life expectancy among some populations reduced by almost 20 years. As we approach the end of the 20th century, further demographic changes are underway with, for the first time in recent human history, a slowing down of world population growth. Nonetheless, world population is projected to grow from 6 billion currently to about 9.4 billion by 2050 (medium fertility assumption), with ageing emerging as the most pressing demographic issue facing humanity in the millenium.
Secretion of urokinase and plasminogen activator inhibitor-1 by normal colonic epithelium in vitro.
Authors: P Gibson, O Rosella, G Rosella, G Young
Journal: Gut (1994)

Urokinase is a neutral protease whose major site of action is the external surface of the plasma membrane of cells and whose major function seems to be modulation of cell adhesion, such as that which occurs during cell migration. This study aimed to determine whether colonic epithelium is involved with the urokinase system. The contents of urokinase and one of its specific inhibitors, plasminogen activator inhibitor-1, were measured in culture supernatant and cell homogenates of isolated human colonic crypt cells. The amounts of both factors increased in supernatants over 24 hours, and approximately twice the amount was found in supernatants than in autologous cell homogenates. The secretion of both factors was similar in serum free and serum containing media. Northern blot analysis showed that messenger ribonucleic acid specific for urokinase and plasminogen activator inhibitor-1 was present in colonic crypt cells and that expression over 18 hours of culture was increased 12 fold for urokinase type plasminogen activator and two to fourfold for the inhibitor compared with values found in autologous freshly isolated cells. Urokinase activity was detected in crypt cell homogenates and supernatants indicating that it was present in excess of its inhibitors. Control experiments indicated that the epithelial cells themselves were responsible for the observations and excluded artefactual effects of the isolation procedure. In conclusion, isolated human colonic epithelial cells secrete urokinase and at least one of its specific inhibitors. Further investigation of the role of urokinase in the physiology and pathophysiology of colonic epithelium is indicated.
Accelerated Evolution of Morph-Biased Genes in Pea Aphids
Authors: Swapna R. Purandare, Ryan D. Bickel, Julie Jaquiery, Claude Rispe, Jennifer A. Brisson
Journal: Molecular Biology and Evolution (2014)

Phenotypic plasticity, the production of alternative phenotypes (or morphs) from the same genotype due to environmental factors, results in some genes being expressed in a morph-biased manner. Theoretically, these morph-biased genes experience relaxed selection, the consequence of which is the buildup of slightly deleterious mutations at these genes. Over time, this is expected to result in increased protein divergence at these genes between species and a signature of relaxed purifying selection within species. Here we test these theoretical expectations using morph-biased genes in the pea aphid, a species that produces multiple morphs via polyphenism. We find that morph-biased genes exhibit faster rates of evolution (in terms of dN/dS) relative to unbiased genes and that divergence generally increases with increasing morph bias. Further, genes with expression biased toward rarer morphs (sexual females and males) show faster rates of evolution than genes expressed in the more common morph (asexual females), demonstrating that the amount of time a gene spends being expressed in a morph is associated with its rate of evolution. And finally, we show that genes expressed in the rarer morphs experience decreased purifying selection relative to unbiased genes, suggesting that it is a relaxation of purifying selection that contributes to their faster rates of evolution. Our results provide an important empirical look at the impact of phenotypic plasticity on gene evolution.
Pressure releases a transferable endothelial contractile factor in cat cerebral arteries.
Authors: D R Harder, C Sanchez-Ferrer, K Kauser, W J Stekiel, G M Rubanyi
Journal: Circulation Research (1989)

When exposed to an increasing transmural pressure, middle cerebral arteries of the cat exhibit reduction of internal diameter which is mediated by vascular muscle cell depolarization. This laboratory has recently demonstrated that this "pressure-induced" activation is dependent upon the presence of an intact endothelium. The present studies were undertaken to determine if this phenomenon is due to inhibition of tonically released endothelium-derived relaxing factors (EDRF) or release of a contractile substance. When cerebral arterial segments were pressurized to between 40 and 160 mm Hg there was 13.2% reduction in internal diameter accompanied by significant muscle cell depolarization from -53 +/- 2.7 to -22 +/- 1.4 mV. There was a significant positive correlation between the delta Em and step increases in transmural pressure. These excitatory responses were lost and vessels dilated to pressure when the endothelium was removed. Upon exposing the denuded vessel to a pressurized intact donor, the denuded vessel recovered its ability to contract and depolarize suggesting that a contractile substance might be released from the vascular endothelium upon pressurization. The EDRF antagonist oxyhemoglobin did not alter the excitatory response to pressure in these isolated cerebral arteries further suggesting that the reduction in diameter and muscle cell depolarization results from the release of a contractile substance from the vascular endothelium and not inhibition of EDRF.