tbuckley/cabot-search huggingface dataset:
Atrial Fibrillation Is Associated With Increased Spontaneous Calcium Release From the Sarcoplasmic Reticulum in Human Atrial Myocytes
Authors: Leif Hove-Madsen, Anna Llach, Antoni Bayes-Genís, Santiago Roura, Enrique Rodriguez Font, Alejandro Arís, Juan Cinca
Journal: Circulation (2004)

Background— Spontaneous Ca 2+ release from the sarcoplasmic reticulum (SR) can generate afterdepolarizations, and these have the potential to initiate arrhythmias. Therefore, an association may exist between spontaneous SR Ca 2+ release and initiation of atrial fibrillation (AF), but this has not yet been reported. Methods and Results— Spontaneous Ca 2+ release from the SR, manifested as Ca 2+ sparks and Ca 2+ waves, was recorded with confocal microscopy in atrial myocytes isolated from patients with and those without AF. In addition, the spontaneous inward current associated with Ca 2+ waves was measured with the use of the perforated patch-clamp technique. The Ca 2+ spark frequency was higher in 8 patients with AF than in 16 patients without (6.0±1.2 versus 2.8±0.8 sparks/mm per second, P &lt;0.05). Similarly, the spontaneous Ca 2+ wave frequency was greater in patients with AF (2.8±0.5 versus 1.1±0.3 waves/mm per second, P &lt;0.01). The spontaneous inward current frequency was also higher in 10 patients with AF than in 13 patients without this arrhythmia (0.101±0.028 versus 0.031±0.007 per second, P &lt;0.05, at a clamped potential of −80 mV). In contrast, both the Ca 2+ released from the SR and the Na + -Ca 2+ exchange rate induced by a rapid caffeine application were comparable in patients with and without AF. Conclusions— The observed increase in spontaneous Ca 2+ release in patients with AF probably is due to an upregulation of the SR Ca 2+ release channel activity, which may contribute to the development of AF.
Structure and function relationships of the respiratory muscles
Authors: J Sauleda, J Gea, M Orozco-Levi, J Corominas, J Minguella, C Aguar, J Broquetas, AG Agusti
Journal: European Respiratory Journal (1998)

Potential relationships between the structure of the diaphragm and external intercostals and several indices of respiratory muscle function, lung function and nutrition in 27 patients (61+/-10 yrs of age) subjected to thoracotomy as a result of a lung neoplasm have been investigated. Prior to surgery the nutritional status of the patients was assessed and lung function (spirometry, lung volumes, transfer factor of the lungs for carbon monoxide, arterial blood gases) and respiratory muscle function (maximal inspiratory pressure (MIP) and diaphragmatic function were measured). Biopsies of the diaphragm (and external intercostals) were obtained during surgery. On average, patients showed mild airflow limitation (forced expiratory volume in one second (FEV1), 70+/-14% of predicted value, FEV1/forced vital capacity (FVC), 70+/-9%) with some air trapping (residual volume (RV), 139+/-50% pred) and normal gas exchange (arterial oxygen tension (Pa,O2), 11.3+/-1.33 kPa (85+/-10 mmHg)) and arterial carbon dioxide tension (Pa,CO2) 5.4+/-0.5 kPa (40.6+/-4 mmHg). MIP was 77+/-25% pred; maximal transdiaphragmatic pressure was 90+/-27 cmH2O. Most morphometric measurements of the diaphragm and external intercostals were within the range of values reported previously in other skeletal muscles. The size of the fibres of these two respiratory muscles was positively related (p&lt;0.05) to MIP (% pred). There were no significant relationships between the structure of both muscles and nutritional status or any index of lung function. In conclusion, in the population studied, the fibre size of the diaphragm and external intercostals appears to relate to their ability to generate force.
Atheroprotective Effects of Alum Are Associated With Capture of Oxidized LDL Antigens and Activation of Regulatory T Cells
Authors: Maria Wigren, Daniel Bengtsson, Pontus Dunér, Katarina Olofsson, Harry Björkbacka, Eva Bengtsson, Gunilla Nordin Fredrikson, Jan Nilsson
Journal: Circulation Research (2009)

The immune system represents a promising novel target for prevention of atherosclerosis. Several pilot vaccines that reduce atherosclerosis in experimental animals have been developed. The aluminum hydroxide adjuvant Alum has been shown to have antiatherogenic properties in itself, suggesting that it may be a suitable adjuvant in possible future atherosclerosis vaccines. To characterize the immune pathways mediating this protection, we treated wild-type C57BL/6 and Apoe(-)(/)(-) mice with Alum or PBS. Analyses of splenocytes isolated from 12-week-old mice demonstrated that Alum increased the presence of CD4(+)CD25(+)FoxP3(+) regulatory T cells and downregulated the expression of T cell activation markers CD28 and ICOS in Apoe(-)(/)(-) mice but not in C57BL/6 wild-type mice. A similar immunosuppressive phenotype was found also in 25-week-old Apoe(-)(/)(-) mice and was associated with reduced atherosclerosis. Alum precipitates recovered from the injection site of Apoe(-)(/)(-) mice contained antigens derived from oxidized LDL. These findings demonstrate that treatment of Apoe(-)(/)(-) mice with Alum results in an increase of regulatory T cells and suggest that these are activated by tolerogenic antigen-presenting cells presenting oxidized LDL antigens. Our findings provide improved mechanistic understanding of the atheroprotective properties of aluminum hydroxide adjuvants but also point to the importance of determining if hypercholesterolemia may compromise the efficacy of Alum-containing vaccines used clinically today.
Risk stratification for 1 year survival based on characteristics identified in the early hours of acute myocardial infarction. The Western Washington Intracoronary Streptokinase Trial.
Authors: M L Stadius, K Davis, C Maynard, J L Ritchie, J W Kennedy
Journal: Circulation (1986)

We evaluated the relationship between baseline factors defined at 4.6 +/- 2.1 hr after onset of acute myocardial infarction and 1 year survival in 245 patients entered in the Western Washington Intracoronary Streptokinase Trial. Univariate statistics identified a significant relationship between 10 of these factors and survival. Multivariate analysis identified three factors as being most closely related to survival: (1) left ventricular ejection fraction (LVEF) (p less than .0001), (2) treatment with streptokinase (p = .03), and (3) location of infarction (p = .04). Mathematic models based on this analysis and applied to our patients identified high- and low-risk subgroups for 1 year mortality. Patients receiving standard, not interventional, therapy with anterior infarction and an LVEF of 50% or less and those with inferior infarction and an LVEF of 39% or less comprised the high-risk group. For patients receiving standard therapy, 1 year mortality was 41% in the high-risk group and 4% in the low-risk group. The models illustrated the magnitude of benefit of streptokinase treatment and achievement of complete reperfusion for those at low and high risk. We conclude that LVEF determined in the first hours of acute myocardial infarction is the most important of all baseline factors for prediction of 1 year survival. Mathematic models based on left ventricular function measured as ejection fraction are useful for risk stratification in this setting.
Prognostic significance of high hyperdiploid and triploid/tetraploid adult acute myeloid leukemia
Authors: Vladimir Lazarevic, Aldana Rosso, Gunnar Juliusson, Petar Antunovic, Åsa Rangert‐Derolf, Sören Lehmann, Lars Möllgård, Bertil Uggla, Lovisa Wennström, Anders Wahlin, Martin Höglund, Bertil Johansson
Journal: American Journal of Hematology (2015)

To ascertain the clinical implications of high hyperdiploid (HH; 49–65 chromosomes) and triploid/tetraploid (TT; &gt;65 chromosomes) adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry. Of the 3,654 cytogenetically informative cases diagnosed between January 1997 and May 2014, 68 (1.9%) were HH ( n = 50)/TT ( n = 18). Patients with HH/TT were older than those with intermediate risk (IR) AML (median 71 years vs. 67 years; P = 0.042) and less often had de novo AML (63% vs. 79%; P = 0.004); no such differences were observed between HH/TT and complex karyotype (CK) AML. The overall survival (OS) was similar between patients with HH/TT and CK AML (median 0.9 years vs. 0.6 years; P = 0.082), whereas OS was significantly longer (median 1.6 years; P = 0.028) for IR AML. The OS was shorter for cases with HH than with TT (median 0.6 years vs. 1.4 years; P = 0.032) and for HH/TT AMLs with adverse abnormalities (median 0.8 years vs. 1.1 years; P = 0.044). In conclusion, HH/TT AML is associated with a poor outcome, but chromosome numbers &gt;65 and absence of adverse aberrations seem to translate into a more favorable prognosis. Thus, HH/TT AMLs are clinically heterogeneous and should not automatically be grouped as high risk.Am. J. Hematol. 90:800–805, 2015. © 2015 Wiley Periodicals, Inc.
Maternal Exposure to Particulate Air Pollution and Term Birth Weight: A Multi-Country Evaluation of Effect and Heterogeneity
Authors: Payam Dadvand, Jennifer Parker, Michelle L. Bell, Matteo Bonzini, Michael Brauer, Lyndsey A. Darrow, Ulrike Gehring, Svetlana V. Glinianaia, Nelson Gouveia, Eun-hee Ha, Jong Han Leem, Edith H. van den Hooven, Bin Jalaludin, Bill M. Jesdale, Johanna Lepeule, Rachel Morello-Frosch, Geoffrey G. Morgan, Angela Cecilia Pesatori, Frank H. Pierik, Tanja Pless-Mulloli, David Q. Rich, Sheela Sathyanarayana, Juhee Seo, Rémy Slama, Matthew Strickland, Lillian Tamburic, Daniel Wartenberg, Mark J. Nieuwenhuijsen, Tracey J. Woodruff
Journal: Environmental Health Perspectives (2013)

Background: A growing body of evidence has associated maternal exposure to air pollution with adverse effects on fetal growth; however, the existing literature is inconsistent.Objectives: We aimed to quantify the association between maternal exposure to particulate air pollution and term birth weight and low birth weight (LBW) across 14 centers from 9 countries, and to explore the influence of site characteristics and exposure assessment methods on between-center heterogeneity in this association.Methods: Using a common analytical protocol, International Collaboration on Air Pollution and Pregnancy Outcomes (ICAPPO) centers generated effect estimates for term LBW and continuous birth weight associated with PM10 and PM2.5 (particulate matter ≤ 10 and 2.5 µm). We used meta-analysis to combine the estimates of effect across centers (~ 3 million births) and used meta-regression to evaluate the influence of center characteristics and exposure assessment methods on between-center heterogeneity in reported effect estimates.Results: In random-effects meta-analyses, term LBW was positively associated with a 10-μg/m3 increase in PM10 [odds ratio (OR) = 1.03; 95% CI: 1.01, 1.05] and PM2.5 (OR = 1.10; 95% CI: 1.03, 1.18) exposure during the entire pregnancy, adjusted for maternal socioeconomic status. A 10-μg/m3 increase in PM10 exposure was also negatively associated with term birth weight as a continuous outcome in the fully adjusted random-effects meta-analyses (–8.9 g; 95% CI: –13.2, –4.6 g). Meta-regressions revealed that centers with higher median PM2.5 levels and PM2.5:PM10 ratios, and centers that used a temporal exposure assessment (compared with spatiotemporal), tended to report stronger associations.Conclusion: Maternal exposure to particulate pollution was associated with LBW at term across study populations. We detected three site characteristics and aspects of exposure assessment methodology that appeared to contribute to the variation in associations reported by centers.
Sarcalumenin alleviates stress-induced cardiac dysfunction by improving Ca2+ handling of the sarcoplasmic reticulum
Authors: Miei Shimura, Susumu Minamisawa, Hiroshi Takeshima, Qibin Jiao, Yunzhe Bai, Satoshi Umemura, Yoshihiro Ishikawa
Journal: Cardiovascular Research (2007)

Sarcalumenin (SAR) is a Ca2+-binding protein expressed in the longitudinal sarcoplasmic reticulum (SR) of striated muscle cells. Although its Ca2+-binding property is similar to that of calsequestrin, its role in the regulation of Ca2+ cycling remains unclear. To investigate whether SAR plays an important role in maintaining cardiac function under pressure overload stress, SAR-knockout (SAR-KO) mice were subjected to transverse aortic constriction (TAC). To examine the relation of SAR with cardiac type of SR Ca2+ pump, SERCA2a, we designed cDNA expression using cultured cells. We found that SAR expression was significantly downregulated in hypertrophic hearts from three independent animal models. SAR-KO mice experienced higher mortality than did wild-type (WT) mice after TAC. TAC significantly downregulated SERCA2a protein but not mRNA in the SAR-KO hearts, whereas it minimally did so in hearts from WT mice. Accordingly, SR Ca2+ uptake and cardiac function were significantly reduced in SAR-KO mice after TAC. Then we found that SAR was co-immunoprecipitated with SERCA2a in cDNA-transfected HEK293T cells and mouse ventricular muscles, and that SERCA2a-mediated Ca2+ uptake was augmented when SAR was co-expressed in HEK293T cells. Furthermore, SAR significantly prolonged the half-life of SERCA2a protein in HEK293T cells. These findings suggest that functional interaction between SAR and SERCA2a enhances protein stability of SERCA2a and facilitates Ca2+ sequestration into the SR. Thus the SAR-SERCA2a interaction plays an essential role in preserving cardiac function under biomechanical stresses such as pressure overload.
Should Pathologists Routinely Report Prostate Tumour Volume? The Prognostic Value of Tumour Volume in Prostate Cancer
Authors: Tineke Wolters, Monique J. Roobol, Pim J. van Leeuwen, Roderick C.N. van den Bergh, Robert F. Hoedemaeker, Geert J.L.H. van Leenders, Fritz H. Schröder, Theodorus H. van der Kwast
Journal: European Urology (2009)
The planar mosaic fails to account for spatially directed action
Authors: Roberta L. Klatzky, Nicholas A. Giudice
Journal: Behavioral and Brain Sciences (2013)

Abstract Humans' spatial representations enable navigation and reaching to targets above the ground plane, even without direct perceptual support. Such abilities are inconsistent with an impoverished representation of the third dimension. Features that differentiate humans from most terrestrial animals, including raised eye height and arms dedicated to manipulation rather than locomotion, have led to robust metric representations of volumetric space.
Achilles tendon thickness, ultrasound signs and symptoms in skaters, gymnasts, elite soccer players, club athletes and healthy sedentary adults - a cross-sectional study
Authors: M Perry, D Morrissey, C Emerson, R Teatino, Z Shaikh, S Mitchell, G O'Driscoll, M Ahmad, N Maffulli
Journal: British Journal of Sports Medicine (2011)

Background Little is known about differences between various sports in terms of Achilles tendon pathology and ultrasonographic (US) findings. An improved knowledge of these differences may help to shed light on possible aetiological factors and guide multi-sport sports medicine support. Aim The aim of this study was to compare Achilles tendon pathology, ultrasound signs and mid-tendon thickness between healthy sedentary controls, gymnasts, skaters, athletes and soccer players. Methodology 111 controls, 40 elite gymnasts/tumblers, 17 elite skaters, 25 elite soccer players and 25 club athletes of mean (SD) age 21.7 (10) years were recruited. The existence of lifetime and present Achilles tendon symptoms were recorded. Mid tendon longitudinal thickness, hypoechoic areas and neovascularisation were determined with high-resolution ultrasound. χ 2 tests were used to compare sports groups for pathology and US signs, and ANCOVA for tendon morphology. Results Both tendons from each participant were included in the analysis. Groups differed in terms of the existence of present symptoms (p&lt;0.001), symptoms ever (p&lt;0.001), hypoechoic areas (p&lt;0.001) and neovascularity (p&lt;0.001). After adjustment for gender, age, lifetime Achilles pathology, height and weight, the groups also differed (p&lt;0.001) in mid tendon thickness (table 1). Posthoc tests showed significant differences in thickness between tendons of controls and gymnasts, controls and soccer players, gymnasts and skaters, gymnasts and athletes, soccer players and skaters, and soccer players and athletes. Controls Gymnasts Skaters Soccer players Athletes Present symptoms (% of tendons) 1.4 15 0 0 8 Past symptoms (% of tendons) 7.2 35 11.8 18 42 Hypoechoic areas (% of tendons) 5 10 0 58 11 Neovascularisation (% of tendons) 0.5 3.8 0 14 20 Mid tendon thickness* (cm) 0.48 (0.01) 0.53 (0.01) 0.437 (0.03) 0.546 (0.02) 0.480 (0.02) * Estimated marginal mean (SE), adjusted to age 21.7, height 167.7cm and weight 62.8kg. Conclusion There were considerable intersport differences in Achilles tendon pathology and ultrasound findings. Gymnastics, athletics and soccer appeared to have higher risk of Achilles tendinopathy symptoms and ultrasound signs than skaters and controls, implying more vigilance in these sports. Gymnasts and soccer players also have greater tendon thickness, which may be related to greater pathology as all participants with present symptoms had greater tendon thickness (p=0.04).
High-Dose Chemotherapy for Recurrent Ovarian Germ Cell Tumors
Authors: Natraj Reddy Ammakkanavar, Daniela Matei, Rafat Abonour, Lawrence H. Einhorn
Journal: Journal of Clinical Oncology (2014)

Thirteen patients with recurrent malignant ovarian germ cell tumors (MOGCT) were treated with salvage highdose chemotherapy (HDCT) from 1990 to 2013.All patients had experienced disease progression after standard cisplatin combination therapy.Patients treated with HDCT as initial salvage treatment for platinum sensitive disease (progression-free interval Ͼ 4 weeks) received one cycle of vinblastine, ifosfamide, and cisplatin (VeIP).HDCT consisted of tandem courses of carboplatin 700 mg/m 2 and etoposide 750 mg/m 2 intravenously daily for 3 consecutive days, followed by stem-cell infusion. 1The second course of HDCT was started after hematopoietic recovery, usually 3 to 4 weeks after the first course.Platinum-refractory disease was defined as serologic or radiographic progression within 4 weeks of prior platinum combination chemotherapy.Complete remission (CR) was defined as no clinically or radiographically detectable disease and normal serum human chorionic gonadotropin and ␣-fetoprotein for at least 4 weeks.Overall survival was measured from initiation of HDCT to last date of follow-up or death.Patient characteristics are shown in Table 1.Median age was 26 years (range, 14 to 47).Eleven patients had yolk sac histology.Eight
Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary heart disease (VTACH): a multicentre randomised controlled trial
Authors: Karl-Heinz Kuck, Anselm Schaumann, Lars Eckardt, Stephan Willems, Rodolfo Ventura, Etienne Delacrétaz, Heinz-Friedrich Pitschner, Josef Kautzner, Burghard Schumacher, Peter S Hansen
Journal: The Lancet (2010)
Fluorescent Probes for Live-Cell RNA Detection
Authors: Gang Bao, Won Jong Rhee, Andrew Tsourkas
Journal: Annual Review of Biomedical Engineering (2009)

Commonly used techniques for analyzing gene expression, such as polymerase chain reaction (PCR), microarrays, and in situ hybridization, have proven invaluable in understanding RNA processing and regulation. However, these techniques rely on the use of lysed and/or fixed cells and are therefore limited in their ability to provide important spatial-temporal information. This has led to the development of numerous techniques for imaging RNA in living cells, some of which have already provided important insight into the dynamic role RNA plays in dictating cell behavior. Here we review the fluorescent probes that have allowed for RNA imaging in living cells and discuss their utility and limitations. Common challenges faced by fluorescent probes, such as probe design, delivery, and target accessibility, are also discussed. It is expected that continued advancements in live cell imaging of RNA will open new and exciting opportunities in a wide range of biological and medical applications.
Nitrite Regulates Hypoxic Vasodilation via Myoglobin-Dependent Nitric Oxide Generation
Authors: Matthias Totzeck, Ulrike B. Hendgen-Cotta, Peter Luedike, Michael Berenbrink, Johann P. Klare, Heinz-Juergen Steinhoff, Dominik Semmler, Sruti Shiva, Daryl Williams, Anja Kipar, Mark T. Gladwin, Juergen Schrader, Malte Kelm, Andrew R. Cossins, Tienush Rassaf
Journal: Circulation (2012)

Hypoxic vasodilation is a physiological response to low oxygen tension that increases blood supply to match metabolic demands. Although this response has been characterized for >100 years, the underlying hypoxic sensing and effector signaling mechanisms remain uncertain. We have shown that deoxygenated myoglobin in the heart can reduce nitrite to nitric oxide (NO·) and thereby contribute to cardiomyocyte NO· signaling during ischemia. On the basis of recent observations that myoglobin is expressed in the vasculature of hypoxia-tolerant fish, we hypothesized that endogenous nitrite may contribute to physiological hypoxic vasodilation via reactions with vascular myoglobin to form NO·.We show in the present study that myoglobin is expressed in vascular smooth muscle and contributes significantly to nitrite-dependent hypoxic vasodilation in vivo and ex vivo. The generation of NO· from nitrite reduction by deoxygenated myoglobin activates canonical soluble guanylate cyclase/cGMP signaling pathways. In vivo and ex vivo vasodilation responses, the reduction of nitrite to NO·, and the subsequent signal transduction mechanisms were all significantly impaired in mice without myoglobin. Hypoxic vasodilation studies in myoglobin and endothelial and inducible NO synthase knockout models suggest that only myoglobin contributes to systemic hypoxic vasodilatory responses in mice.Endogenous nitrite is a physiological effector of hypoxic vasodilation. Its reduction to NO· via the heme globin myoglobin enhances blood flow and matches O(2) supply to increased metabolic demands under hypoxic conditions.
Ombudsmen find NHS trust and council guilty of "shocking" failings over care of man with Down's syndrome
Authors: A. O'Dowd
Journal: BMJ (2011)

Traumatic brain injury (TBI) increases susceptibility to Alzheimer9s disease (AD), but it is not known how TBI contributes to the onset or progression of this common late life dementia. To address this question, we studied neuropathological and behavioral consequences of single versus repetitive mild TBI (mTBI) in transgenic (Tg) mice (Tg2576) that express mutant human Aβ precursor protein, and we demonstrate elevated brain Aβ levels and increased Aβ deposition. Nine-month-old Tg2576 and wild-type mice were subjected to single (<i>n</i> = 15) or repetitive (<i>n</i> = 39) mTBI or sham treatment (<i>n</i> = 37). At 2 d and 9 and 16 weeks after treatment, we assessed brain Aβ deposits and levels in addition to brain and urine isoprostanes generated by lipid peroxidation in these mice. A subset of mice also was studied behaviorally at 16 weeks after injury. Repetitive but not single mTBI increased Aβ deposition as well as levels of Aβ and isoprostanes only in Tg mice, and repetitive mTBI alone induced cognitive impairments but no motor deficits in these mice. This is the first experimental evidence linking TBI to mechanisms of AD by showing that repetitive TBI accelerates brain Aβ accumulation and oxidative stress, which we suggest could work synergistically to promote the onset or drive the progression of AD. Additional insights into the role of TBI in mechanisms of AD pathobiology could lead to strategies for reducing the risk of AD associated with previous episodes of brain trauma and for preventing progressive brain amyloidosis in AD patients.