tbuckley/cabot-search huggingface dataset:
High resolution and dynamic imaging of biopersistence and bioreactivity of extra and intracellular MWNTs exposed to microglial cells
Authors: Angela E. Goode, Daniel A. Gonzalez Carter, Michael Motskin, Ilse S. Pienaar, Shu Chen, Sheng Hu, Pakatip Ruenraroengsak, Mary P. Ryan, Milo S.P. Shaffer, David T. Dexter, Alexandra E. Porter
Journal: Biomaterials (2015)
Abstract 4274: Retrograde Ascending Aortic Dissection During or After Thoracic Aortic Stent-Graft Placement- Insights from the European Registry on EVAR Complications (EUREC)
Authors: Holger Eggebrecht, Matt Thompson, Herve Rousseau, Martin Czerny, Lars Lönn
Journal: Circulation (2008)

Background: Thoracic endovascular aortic repair (TEVAR) is increasingly applied in the treatment of aortic dissections and aneurysms. Single center reports have addressed retrograde ascending aortic dissection (rAAD) as a potentially lethal complication unique to TEVAR. We used data from a European multi-center registry to determine possible etiological factors and outcomes of this dreadful complication. Methods: So far 15 European sites and 1 Chinese center are contributing to the European Registry on EVAR Complications (EUREC) which is an open, independent, ongoing multi-center registry. Between 01/1998 and 05/2008 these centers performed a total of 3074 TEVAR procedures. Results: 33 rAAD cases (56.3±11.6 yrs, 20 males) were reported (incidence 1.1%). Indications for TEVAR were: acute type B dissection (n=17), chronic dissection (n=10), thoracic aneurysm (n=4), and aortic ulcer (n=1). 20 procedures were performed as emergency TEVAR. Stent-grafts with proximal bare springs were used in 26/33 (79%) cases. Additional balloon inflations were performed in 6 (18%) cases. rAAD occurred intraoperatively (n=5, 15%), during the index hospitalization (n=7, 21%), and during follow-up (n=21, 64%). 9 (27%) patients were asymptomatic, the remaining patients presented with acute chest pain (n=11, 33%), syncope (n=10, 30%), or sudden death (n=5, 15%). Emergency or elective surgical repair was performed in 19 and 4 patients, respectively. Conservative therapy was chosen in the remaining 10 patients. Outcome was fatal in 14/33 (42%) patients. The most probable cause of rAAD as reported by the investigators was stent-graft induced in 58%, procedure related in 9%, and underlying undiagnosed aortic disease in 15% of patients. In 16/33 patients direct evidence of stent-graft induced rAAD was obtained by surgery or necropsy. Conclusion: Although the incidence of rAAD was low (1.1%) in the present EUREC analysis, it was associated with significant mortality (42%). Patients undergoing TEVAR for type B dissection appeared to be most prone rAAD. As suspected, the majority of rAAD cases was associated with the use of proximal bare spring stent-grafts and in almost half of the patients direct evidence of stent-graft induced injury was obtained from surgery or necropsy.
Abstract 735: Gene Therapy using Fragments of the SCN5A H558R Polymorphism Restores Function of a Brugada Syndrome Mutation
Authors: Lynn Dudash, Steven Poelzing, Isabelle Deschenes
Journal: Circulation (2006)

Brugada Syndrome (BrS) is caused by mutations in the cardiac sodium (Na) channel gene. One such mutation is R282H, which produces a loss of function. We demonstrated that coexpressing the SCN5A pol...
Abstract 3465: The Pharmacogenomic Interaction Between Inhibition of Renin-Angiotensin-Aldosterone System and beta1 Adrenoreceptor Gly389Arg Polymorphism
Authors: Hiroya Mizuno, Hiroshi Sato, Yasuhiko Sakata, Hiroya Kondo, Daisaku Nakatani, Masahiko Shimizu, Shinichiro Suna, Atsushi Hirayama, Masatsugu Hori, Oacis Investigators
Journal: Circulation (2006)
Dengue infection with multiorgan dysfunction: SOFA score, arterial lactate and serum albumin levels are predictors of outcome
Authors: Sameer Jog, Shirish Prayag, Prasad Rajhans, Kapil Zirpe, Subhal Dixit, Lalitha Pillai, Jignesh Shah, Mukund Penurkar, Arjun Kakrani, Ajit Yadav, Kayanoosh Kadapatti, Balasaheb Pawar, Deepak Salunke, Pramod Joshi, Aniruddh Deshpande, Sushma Gurav, Divyesh Patel
Journal: Intensive Care Medicine (2015)
Snapshots from the decade of the brain
Authors: C. Martyn
Journal: BMJ (1998)

The last 10 years of the 20th century have been designated the decade of the brain. But, with the notable exception of the revolution in brain imaging, the explosion of activity in neurobiology has failed to capture the imagination of most doctors. To remedy this, we asked six neuroscientists to write about what interested them most.

If you thought that visual processing was restricted to the striate cortex of the occipital lobes, turn to Adam Zeman’s article (p 1696). More than 30 separate cortical representations of the visual field have now been identified, and positron emission tomography is revealing what each contributes to the analysis of complex visual stimuli. Richard Gregory also discusses vision, though from a different point of view (p 1693). He asks (and suggests an answer) why real time sensory inputs should be associated with conscious perception.

Consciousness, however one defines it, seems to be a property of the brain as a functioning system—not something that resides in individual neurones. Almost the opposite seems to be true of the way the brain keeps track of time. The central circadian clock is localised in the suprachiasmatic nucleus of the hypothalamus, but, as Michael Hastings explains, single nerve cells from this area retain the capacity to show a 24 hour rhythm even when isolated in culture (p 1704).

Ian Deary and Susan Greenfield tackle issues of more immediate clinical relevance. Deary discusses the validity of attempts to measure cognitive ability (p 1701), while Greenfield explores how recent discoveries about central neurotransmitters could be exploited for treating neurodegenerative disease (p 1698).

Understanding how the brain works requires more than knowledge of the intricacies of neuronal connections and neurotransmitters. In the last article Steven Rose points out the limitations of our current reductionist concepts (p 1707). He is especially scathing about the tendency to attribute complicated patterns of human behaviour—homosexuality or aggression, for example—to genetic polymorphisms. Along with A M Daniels’ cow slaughtering piece (p 1728), it provides a salutary warning against triumphalist neuroscientific hype.
Abstract 354: Enhanced Coronary Thrombolysis by Three-dimensional Transthoracic Ultrasound and Intravenous Non-Targeted Microbubbles
Authors: Feng Xie, John Lof, Evan Unger, Terry Matsunaga, Thomas R Porter
Journal: Circulation (2009)

High mechanical index (MI) ultrasound impulses from a diagnostic transducer combined with intravenous (IV) microbubbles (MB) have recanalized vessel thromboses in animal studies. In acute coronary ...
Abstract 18338: Biomaterial Delivery Vehicles Improve Acute Retention of Cells in the Infarcted Heart
Authors: Ellen T Roche, Conn L Hastings, Sarah A Lewin, Dmitry Shvartsman, Yevgeny Brudno, Nikolay V Vasilyev, Fergal J O’Brien, Conor J Walsh, Garry P Duffy, David J Mooney
Journal: Circulation (2013)

Introduction and Hypothesis: Cell delivery to the infarcted heart has emerged as a promising therapy, but is limited by very low acute retention and engraftment of cells. The hypothesis was that acute retention can be improved with a biomaterial carrier, and the study compared several. Methods: Cells were quantified 24 hours post-implantation in a rat myocardial infarct model (Fig. 1a) in five groups (n=8 per group); saline injection (current clinical standard), two injectable gels (alginate and chitosan) and two epicardial patches (alginate and collagen). For injectable groups 60ul of saline or gel containing 400,000 human mesenchymal stem cells was injected intramyocardially in the infarct border zone. 400,000 cells were seeded on alginate or collagen patches, and implanted on the epicardial surface at infarct border zone. At 24 hours, retained cells were quantified with Xenogen imaging system. Hearts were perfused and sectioned to stain for retained cells. Results: All biomaterials significantly improved retention compared to a saline control, with 4.1 and 2.6-fold increases for chitosan and alginate injectables, and 14.2 and 19.3-fold increases achieved with collagen and alginate patches, respectively (Fig. 1b-c). Immunohistochemical analysis qualitatively confirmed these findings (Fig. 1d). Encapsulated/seeded cell survival was assessed in hypoxia/ischemia to further compare biomaterials. Conclusion: Injectable gels and epicardial patches were demonstrated to improve acute retention of cells when compared to a saline control. Injectable gels enable immediate myocardial delivery while epicardial patches facilitate superior retention and could potentially sustain cell delivery over extended periods. These biomaterial approaches should be considered for future cell therapy applications. Figure 1: a) Procedural steps b-c) Cell retention after 24 hours d) Ventricle wall showing DAPI and implanted cells with GFP antibody (green) for each group
Abstract 12672: More Than 40% of Hypertensive Sleep Apnea Turned to Normotensive by Continuous Positive Airway Pressure Therapy Along With More Substantial Benefit in Having Morning Hypertension
Authors: Fumihito Nakayama, Hiroyuki Yoshimine, Yoshitaka Harada, Keigo Miyata, Shiro Yamachika, Koji Maemura, Shinji Seto
Journal: Circulation (2011)

Background: Sleep apnea (SAS) elevates blood pressure (BP) and is one of important causes of resistant hypertension (HT). Continuous positive airway pressure therapy (CPAP) decreases BP in SAS patients. However, the impact of CPAP on BP in hypertensive SAS patients is still obscure. This study is to examine the hypothesis that (1) BP lowering effect of CPAP is more prominent on morning BP than on evening BP in hypertensive SAS patients, and (2) a high percentage of hypertensive SAS patients especially of having morning HT turn to normotensive by CPAP. Methods: Ninety-three hypertensive SAS patients (74 males, 19 females, age 57.0+/-14.1, BMI 27.2+/-5.3) treated by CPAP were included. All patients were undertaken polysomnography before and after CPAP application and measured morning and evening BP in each occasion. CPAP was applied in patients with apnea-hypoxia index (AHI) > 20. Mean duration of CPAP was 32.7+/-26.1 days. Central SAS shared only 2.1% in these patients. HT was defined as SBP of ≥140 and/or...
Abstract 13758: Impact of Chronic Statin Administration on Acetylcholine-Induced Endothelial Dysfunction
Authors: Seong Gyu Yoon, Seung Woon Rha, Byoung Geol Choi, Se Yeon Choi, Amro Elnagar, Sung Il Im, Sun Won Kim, Jin Oh Na, Seong Woo Han, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Circulation (2012)
Congenital toxoplasmosis in France in 2007: first results from a national surveillance system
Authors: I Villena, T Ancelle, C Delmas, P Garcia, A P Brézin, P Thulliez, M Wallon, L King, V Goulet, None Toxosurv network and National Refer
Journal: Eurosurveillance (2010)

When immunocompetent people become infected with the parasite Toxoplasma gondii, the disease is generally asymptomatic. However, transplacental transmission of T. gondii may lead to severe congenital infection including in utero abortion, foetal death, or neurological or ocular damage of the foetus. France has had a national programme to prevent congenital toxoplasmosis since 1978. However, although estimated seroprevalence in pregnant women has fallen from 84% in the 1960s to 44% in 2003, no reliable data have been available on the annual number of cases of congenital toxoplasmosis or the severity of infection. In 2006, the French National Institute for Public Health Surveillance (Institut de Veille Sanitaire) and the National Reference Centre for Toxoplasmosis recommended that a national laboratory-based surveillance system be used for the surveillance of the disease. In 2007, 31 laboratories reported at least one congenital case through the surveillance system, giving a total of 272 cases. A total of 11 terminations of pregnancy were reported (six abortions and five foetal deaths). Of the live-born cases, 206 were asymptomatic, 28 were symptomatic and seven had a severe form of the disease. As there were 818,700 births in France and French overseas departments in 2007, the overall prevalence of congenital toxoplasmosis observed that year was 3.3 (95% confidence interval (CI): 2.9 to 3.7) per 10,000 live births and the incidence rate of the disease at birth was 2.9 (95% CI: 2.5 to 3.2) per 10,000 live births; the estimated incidence rate of symptomatic congenital toxoplasmosis was 0.34 (95% CI: 0.2 to 0.5) cases per 10,000 live births.
Abstract 9862: Rearrangement of Myocardial Deformation to Preserve Left Ventricular Ejection Performance in Chronic Aortic Regurgitation
Authors: Yoshihiro Seo, Tomoko Ishizu, Noriko Iida, Kazutaka Aonuma
Journal: Circulation (2011)

Background: In chronic aortic regurgitation (AR) patients, rearrangements of left ventricular (LV) wall deformation including contraction and thickening may occur to preserve LV ejection performance in the course of myocardial adaptation to increased systolic wall stress. We assessed transmural rearrangements of myocardial deformation by speckle tracking echocardiography in patients with chronic AR. Methods: We enrolled 90 patients with AR and 53 control subjects. On a LV short-axis B-mode image, total-, inner-half -, and outer-half radial strain (RS) and circumferential strain (CS) at inner, mid, and outer layers were calculated. Longitudinal strain (LS) was calculated on an apical 4-chamber image. Three components of end-systolic wall stress (ESS) were calculated: midwall circumferential (ESSc), meridional (ESSm), and inner radial (ESSr). AR severity was classified as moderate in 31 patients, severe with preserved LVEF ≥50% (severe ARpEF) in 42 patients, and severe with depressed LVEF &lt;50% (severe ARdEF) in 17 patients. Results: LS was decreased even in the moderate AR group with normal ESSm. Inner-RS progressively decreased with increases of ESSr; however, outer-RS in the moderate and severe ARpEF groups was higher than that in the control group. Consequently, total-RS was preserved even in the severe ARpEF group with increased ESSr. Inner-CS was lower in the severe ARpEF group than in the control and moderate AR groups, however, outer-CS was higher in the severe ARpEF group than in the control group. All strain parameters were lower in the severe ARdEF group with dramatically increased ESS than in other groups. In 29 patients with aortic valve replacement (AVR), total-RS and outer-RS were significantly decreased after AVR. The ratio of inner-RS to outer-RS significantly increased after AVR and did not differ from that in the control group. Conclusions: Transmural strain analysis revealed rearrangements of wall deformation in the course of adaptation to increased ESS in patients with AR. As a distinctive rearrangement, subendocardial dysfunction accompanied by increased wall thickening in the subepicardium may indicate vertical compensation of wall thickening to preserve LVEF.
Neutralizing antibody against FGFR3 shows anti-tumor effects in multiple tumor models in vivo
Authors: Roberto DiRenzo, Maria Malabunga, Marie Prewett, Rajiv Bassi, David Surguladze, Juqun Shen, James Tonra, Paul Kussie, Haijun Sun
Journal: Cancer Research (2007)

2080  Dysregulation of FGFR3 signaling has been observed in certain cancers: in Urothelial Cell Carcinoma (UCC) FGFR3 expression is higher in tumor cells compared to normal tissue; in Multiple Myeloma (MM) t(4;14)(p16;q32)-translocation leads to FGFR3 over-expression. Activating mutations of the receptor are common in both cancer types and some of these mutations are capable of transforming normal cells. We have shown that a neutralizing antibody against FGFR3, IMC-D11, inhibits FGFR3 signaling in vitro. Here we tested the anti-tumor activity of IMC-D11 in mouse xenograft models. A range of tumor cell lines, including UCC and MM, were screened for FGFR3 expression by flow cytometry and RT-PCR. High FGFR3 expression was confirmed in RT-112, RT-4, OPM-2 (harboring an activating K650E point mutation in FGFR3), GEO, and Fadu. Treating the tumor cells with FGF1 and/or FGF9 led to up-regulation of phospho-Erk1/2, phospho-Akt, and/or phospho-p38; suggesting FGFR3 signaling may play a role in tumor growth and survival. IMC-D11 significantly inhibited growth of these tumor cells in mouse xenografts. When combined with cytoxic agents, the antibody produced enhanced anti-tumor effects in RT-112, RT-4 and Fadu xenografts. In contrast, the antibody showed no effect on FGFR3-null PC-3 tumors in an orthotopic xenograft model. Our study suggests that IMC-D11 inhibits xenograft tumor growth by specifically down-modulating FGFR3 mediated mitogenic and/or survival signaling in tumor cells and that FGFR3 may be a viable therapeutic target for not only UCC and MM, but also other tumors that express high levels of the receptor.
Abstract 4734: Echodynamography is a Novel Useful Technique in Assessing Inertia Force of Late Systolic Aortic Flow and Left Ventricular Early Diastolic Function
Authors: Kazuaki Wakami, Nobuyuki Ohte, Chika Kato, Kaoru Asada, Toshihiko Goto, Hidekatsu Fukuta, Tatsuya Ito, Seiji Mukai, Syogo Suzuki, Genjiro Kimura
Journal: Circulation (2008)

We previously reported that the inertia force (IF) of the blood flowing out of left ventricle (LV) during late systolic phase produces greater LV elastic recoil force and brings faster LV relaxation. Echodynamography (ALOKA) is a novel technique that enables us to obtain the flow velocity vector from conventional color Doppler velocity data on the range of interest at any phase of cardiac cycle without angle dependency. We investigated whether the flow velocity vector obtained at LV outflow tract (LVOT) in late systole had a relation with IF and invasively obtained LV relaxation parameters. Method: Study subjects were consecutive 26 patients who underwent diagnostic cardiac catheterization and conventional color Doppler imaging on the same day. Color Doppler image was acquired in the apical 3-chamber view. The analyses for flow velocity vector were performed offline using an echo image analyzer. The late systolic velocity of the blood flowing was obtained as an average value of the L VOT (V LVOT −late systole). LV pressure was obtained using a catheter-tipped micromanometer. From the recorded pressure waves, first derivative of LV pressure (dP/dt) and a time constant τ of LV pressure decay during isovolumic relaxation were calculated. From LV pressure-dP/dt relationships (phase loop), IF was determined. Results: A significant positive correlation was observed between the V LVOT -late systole and IF (r=0.75, p&lt;0.0001). The V LVOT -late systole also had significant correlations both with peak negative dP/dt (r=0.49, p&lt;0.05) and the time constant τ (r=−0.70, p&lt;0.0001). Conclusion: This study indicates that the V LVOT -late systole, which may be a noninvasive substitute for IF, has significant correlations with the parameters of LV relaxation. Echodynamography is a new useful technique to estimate LV early diastolic function.
Use of high-density SNP-array analysis to identify novel chromosomal abnormalities that predict survival in multiple myeloma
Authors: H. Avet-Loiseau, N. Munshi, C. LI, F. Magrangeas, W. Gouraud, C. Charbonnel, K. C. Anderson, P. Moreau, L. Campion, S. Minvielle
Journal: Journal of Clinical Oncology (2008)

8522 Background: Despite major improvements in the treatment of myeloma over the last decade, disease course is variable due to genetic heterogeneity. Even though cytogenetics is a difficult art in myeloma, chromosomal abnormalities are present in 100% of the patients, and some preliminary data have shown that some chromosomal abnormalities are highly predictive of a short survival. Methods: In order to define the spectrum of unbalanced chromosomal abnormalities in myeloma, we studied a cohort of 192 patients ≤ 65 years of age, homogeneously treated with high dose chemotherapy in the IFM 99 trials, using the Affymetrix 500K SNP arrays. Bone marrow was obtained at diagnosis, and plasma cells were sorted using anti-CD138-coated magnetic beads. In all cases, a plasma cell suspension with a purity > 90% was obtained, and DNA was extracted using standard methods. After labeling, DNA was hybridized on the two Nsp and Sty chips, containing 260,000 SNPs each. Results: As expected, copy number variations were observed in all the cases. The most frequently involved chromosomes were chromosomes 13, 16, 1, 8 and 6. We then performed a prognostic analysis to correlate survival and chromosomal abnormalities. Many previously unreported chromosomal regions were identified. The most frequently lost regions associated with overall survival were 1p, 6q, 8p, 12p, 14q, 16q, 17q, 20p, and 22q. Global analysis revealed a marked heterogeneity in the gains observed in hyperdiploid karyotypes, explaining the inconsistency in the literature regarding the prognostic value of hyperdiploidy. Conclusion: This study represents the largest cohort of patients analyzed with such high-density arrays, enabling the description of a highly confident landscape of chromosomal abnormalities in myeloma. Moreover, since all the 192 patients were treated with a similar high-dose regimen, it allows powerful statistical analysis of the impact of chromosomal gains and losses on response to therapy, event free survival and overall survival. Finally, since all the patients were also annotated for other prognostic parameters such as t(4;14) or beta2-microglobulin, a multivariate prognostic model will be presented. No significant financial relationships to disclose.
Heart Making and Heart Breaking: The Molecular Circuitry of Heart Development, Disease and Regeneration
Authors: Eric Olson
Journal: Circulation (2011)

Heart disease remains the primary cause of morbidity and mortality in the developed world. A major reason for this is that the adult human heart has limited regenerative capacity following injury. The default healing response in the adult heart following myocardial infarction or other disorders that cause loss of heart muscle cells involves replacement of cardiac muscle with fibrous, noncontractile scar tissue. The consequent loss of contractility diminishes cardiac function and ultimately leads to heart failure and death. In recent studies, we found that the hearts of neonatal mice can fully regenerate after partial surgical resection, but this capacity is lost by 7 days of age. We are currently exploring the molecular underpinnings of the neonatal regenerative response of the heart, with the long-term goal of discovering combinations of genes and drugs that promote cardiac repair and regeneration. We are also optimizing strategies for reprogramming of cardiac fibroblasts toward a cardiomyocyte cell fate as a means of replacing heart muscle following myocardial infarction. It has recently become apparent that microRNAs play key roles in modulating the response of the heart to injury. Because individual microRNAs often regulate the expression of multiple target genes with related functions, modulating the expression of a single microRNA can modify complex disease phenotypes. We have identified signature expression patterns of microRNAs associated with diverse cardiovascular disorders, including pathological cardiac hypertrophy, heart failure, myocardial infarction, vascular stenosis and angiogenesis. Gain- and loss-of-function studies in mice have revealed striking functions for these microRNAs in numerous facets of cardiac biology, including the control of sarcomere formation, fibrosis, hypoxia, myocyte survival, cytoskeletal dynamics and erythropoiesis. Disease-inducing microRNAs can be persistently silenced in vivo through systemic delivery of anti-miRs, allowing for therapeutic modulation of disease mechanisms. Recent advances in understanding the mechanisms of cardiac injury and regeneration as well as strategies for promoting cardiac repair through modulation of intrinsic regenerative mechanisms will be discussed.