tbuckley/cabot-search huggingface dataset:
Orthostatic Hypotension as a Prodromal Marker of α-Synucleinopathies
Authors: Jose-Alberto Palma, Lucy Norcliffe-Kaufmann, Horacio Kaufmann
Journal: JAMA Neurology (2018)

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Abstract MP63: Loss of Ideal Blood Pressure in Childhood: Age-specific Emergence of Gender and Race/ethnic Disparities
Authors: Shakia T Hardy, Katelyn M Holliday, Sujatro Chakladar, Joseph C Engeda, Gerardo Heiss, Danyu Lin, Christina M Shay, Donglin Zeng, Christy L Avery
Journal: Circulation (2016)

Introduction: Gender and race/ethnic disparities in the burden of adverse blood pressure (BP) levels in adulthood have origins in childhood. Proper timing of primordial prevention efforts could narrow inequalities in BP trajectories across the life course. Few studies have characterized the ages at which children transition from ideal BP by gender and race/ethnicity, using contemporary multiethnic populations. Methods: We utilized the prevalence of ideal (&lt;90th percentile for SBP and/or DBP), intermediate (90th-95th percentile or SBP ≥120 or DBP ≥80 mm Hg) and poor (&gt;95th percentile for SBP and/or DBP) BP levels among African American (AA), European American (EA), and Mexican American (MA) NHANES participants (2007-2012, n=4,566) to estimate race/ethnic, age (8-19 years), and sex-specific net probabilities of transitioning between levels of BP using novel Markov-type modeling. Results: At age 8, the prevalence of ideal BP differed more by gender than by race/ethnicity, with the prevalence of ideal BP among boys (AA: 87%; EA and MA: 89%) being lower than the prevalence of ideal BP in girls (AA: 92%, EA 94%, MA 96%). From age 8, the magnitude of net declines in ideal BP also varied by gender and race/ethnicity. For example, between ages 8-11, the population of AA boys with ideal BP declined a net 1.6% [95% confidence interval (CI): 1.3-1.8%] annually, net declines that were approximately 25% greater than net declines estimated in EA and MA boys. For all race/ethnic groups, annual net declines in ideal BP among girls were less than half the decline of their male counterparts. Between 12-15 years of age, the largest declines for both genders occurred in AAs (AA boys: 2.1%, 95% CI: 1.7-2.5%; AA girls: 0.9%, 95% CI: 0.7-1.1%). By age 19, the annual net declines in ideal BP increased to approximately 2.9% (95% CI: 2.3-3.5%) and 1.4% (95% CI: 1.1-1.7%) per year for AA boys and AA girls, respectively. These declines, together with earlier net transition patterns widened ideal BP disparities in both boys (AA 68%, EA 73%, MA 75%) and girls (AA 84%, EA 89% MA 93%) at age 19. Conclusions: Disparities in transitions from ideal BP emerge during childhood and early adolescence, with disparate, rapid declines in ideal BP observed in boys and AAs, thus introducing BP disparities. Research emphasizing safe and effective primordial prevention efforts in childhood is necessary to preempt disparities and their maintenance.
Abstract 1342: Mitochondrial dysfunction activates lysosomal-dependent mitophagy selectively in cancer cells
Authors: Thomas Biel, Ashutosh Rao
Journal: Cancer Research (2018)

Abstract Mitochondria-targeted drugs are designed to accumulate in the mitochondrion to modulate metabolism. Triphenylphosphonium (TPP) conjugated agents are a class of mitochondria-targeted drugs that induce mitochondrial dysfunction in cancer cells. Mitochondrial dysfunction is known factor that facilitates the onset of mitophagy. However, the activation of mitophagy to remove drug-induced mitochondrial damage is unknown. Here, we subjected breast MDA-MB-231 cancer cells and MCF-12A noncancerous cells to a series of mitochondria-targeted redox-active agents (MTA) that contain TPP to investigate the onset and activation of autophagy, mitophagy and mitochondrial dysfunction. Collectively, we identified three different MTAs from the series that sequentially damage the mitochondria, enhance autophagic flux, and activate mitophagy selectively in MDA-MB-231 cells. Furthermore, we generated stably expressing mt-mKeima MDA-MB-231 and MCF-12A cell lines to establish a mitophagy flux assay for screening new agents. FACS analysis of mt-mKeima, a pH-sensitive fluorophore, revealed MTAs induced lysosomal dependent mitochondrial degradation and the presence of bafilomycin, a lysosomal inhibitor, suppressed MTA-induced mitophagy. To confirm MTAs induced mitochondrial autophagy, we identified mitochondria located within autophagosomes using confocal microscopy, an endogenous autophagy-related protein complex by coimmunoprecipitation and mitochondrial PINK1 accumulation using immunoblot. These in vitro studies were translated into an in vivo rat SST-2 xenograph breast cancer model to demonstrate that mitochondrial PINK1 accumulates in rat tumor tissue following MitoQ treatment. These data suggest that mitochondria-targeted agents selectively caused mitochondrial depolarization, PINK1 accumulation and mitophagy in MDA-MB-231 cancer cells as compared to MCF-12A noncancerous cells. Citation Format: Thomas Biel, Ashutosh Rao. Mitochondrial dysfunction activates lysosomal-dependent mitophagy selectively in cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1342.
Coexistence of Patent Ductus Arteriosus and Congenital Aortic Valvular Disease
Authors: Herbertmark, Bellejacobson, Dennisonyoung
Journal: Circulation (1958)

Congenital aortic or subaortic stenosis was demonstrated in 7 of 50 patients with patent ductus arteriosus. In addition to the murmurs characteristic of each lesion and diagnostic carotid artery pulse tracings, inordinate enlargement of the left ventricle with a small shunt through the patent ductus should suggest involvement of the aortic valve. The clinical findings associated with this combination of lesions are clear cut and awareness of them should lead to more frequent identification than has been reported previously.
Implementation of the Fifth Link of the Chain of Survival Concept for Out-of-Hospital Cardiac Arrest
Authors: TakashiTagami, KazuhikoHirata, ToshiyukiTakeshige, JunichirohMatsui, MakotoTakinami, MasatakaSatake, ShuichiSatake, TokuoYui, KunihiroItabashi, ToshioSakata, RyoichiTosa, ShigekiKushimoto, HiroyukiYokota, HisaoHirama
Journal: Circulation (2012)

Background—The American Heart Association 2010 resuscitation guidelines recommended adding a fifth link (multidisciplinary postresuscitation care in a regional center) to the previous 4 in the chain of survival concept for out-of-hospital cardiac arrest. Our study aimed to determine the effectiveness of this fifth link. Methods and Results—This multicenter prospective cohort study involved all eligible out-of-hospital cardiac arrest patients in the Aizu region (n=1482, suburban/rural, Fukushima, Japan). Proportions of favorable neurological outcomes were evaluated before (January 2006–April 2008) and after (January 2009–December 2010) the implementation of the fifth link. After implementation, all patients were transported directly from the field to the tertiary-level hospital or secondarily from an outlying hospital to the tertiary-level hospital after restoration of circulation. The tertiary hospital provided intensive postresuscitation care, including appropriate hemodynamic and respiratory management,...
Abstract 18650: Ninjurin1, a Novel Regulatory Factor of Pericytes to Interact With Endothelial Cells, Mediates the Circulation Recovery in the Hind Limb Ischemia
Authors: MotokiMatsuki, Jun-ichiKawabe, TatsuyaAonuma, MakiKabara, AtsushiYamauchi, KoheiShimamura, AkihoMinoshima, NaofumiTakehara, YukihiroSaito, NaoyukiHasebe
Journal: Circulation (2014)

Background: Microvascular maturation/stabilization is crucial phenomenon for patho-physiological situations such as ischemic diseases. Vascular maturation/stabilization is regulated through the interaction between pericytes (PCs) and endothelial cells (ECs). In order to clarify the mechanisms for vascular maturation/stabilization, we detected a novel factor, which is involved in the interaction between PCs and ECs using capillary-derived PCs cell lines, and examined the role of this factor on angiogenesis. Methods and Results: We have established immortalized capillary-derived PCs from temperature sensitive SV40T-antigen-harboring mice. After GFP-expressing PCs were co-incubated with/without the sprouting EC tubes in 3D-gel, GFP-positive cells were collected by FACS and applied to microarray analysis. Ninjurin1 (nerve injured protein; Ninj1) have been selected among several candidate genes, of which expression levels in PCs were changed after interaction with sprouting EC tubes. When expression of Ninj1 i...
Effects of a Specific Endothelin-Converting Enzyme Inhibitor on Cardiac, Renal, and Neurohumoral Functions in Congestive Heart Failure
Authors: AtsuyukiWada, TakayoshiTsutamoto, MasatoOhnishi, MasahideSawaki, DaisukeFukai, YukiharuMaeda, MasahikoKinoshita
Journal: Circulation (1999)

Background—Endothelin (ET)-1 is generated from big ET-1 by endothelin-converting enzyme (ECE). Plasma big ET-1 and ET-1 levels are strongly related to survival in patents with congestive heart failure (CHF). Because selective enzymatic processing of ET-1 formation appears to be an important therapeutic target for CHF, we investigated the acute effects of a specific ECE inhibitor on cardiorenal and endocrine functions in CHF compared with those of a selective ETA receptor antagonist. Methods and Results—CHF was induced in beagle dogs by rapid right ventricular pacing (270 bpm, 14 days). Two incremental doses of a specific ECE inhibitor, FR901533, or a selective ETA receptor antagonist, FR139317 (1 and 3 mg/kg, n=8, respectively), were injected into dogs with CHF. FR901533 and FR139317 decreased mean arterial pressure and pulmonary capillary wedge pressure associated with reduction in systemic and pulmonary vascular resistance. These agents increased cardiac output but did not affect left ventricular fracti...
Abstract 19199: The Effects of Self Efficacy and Social Support on Quality of Life of Patients and Family Caregivers After Coronary Artery Bypass Grafting
Authors: Patricia Thomson, Catherine A Howie, Missok L Chung
Journal: Circulation (2015)

Introduction: Personal and social resources are critical factors in patient recovery after coronary artery bypass grafting (CABG). Family members are an importance source of support for the patient. Because of the importance of interdependent relationships, it is vital to examine associations between self efficacy, social support and quality of life at the dyadic level. No known studies have explored patient’s cardiac self efficacy and family caregiver’s perceptions of patient self efficacy and social support as influences on quality of life in CABG Aims: To examine the effects of patient’s pre-operative cardiac self efficacy and family caregiver’s perceptions of patient self efficacy on their own and their partner’s quality of life after CABG; to examine the effects of patient’s and family caregiver’s preoperative social support on their own and their partner’s quality of life after surgery. Methods: A total of 80 dyads completed questionnaires before and 4 months after CABG. Self-efficacy was assessed using the Cardiac Self Efficacy, social support was assessed using the MOS Social Support Survey, and quality of life assessed using the Short-Form 12 Health Survey. Longitudinal data were analysed using Multilevel modelling regression, the Actor-Partner Interdependence Model with distinguishable dyad regression. Results: Of the 80 dyads, 75 were patient-spouse dyads. Patients were 80% males, aged 64.5 years and family caregivers were 90% females, aged 61.05 years. Patients’ tangible support exhibited an actor e ffect on their mental health,indicating low tangible support pre-operatively predicted their poorer mental health 4 months after CABG (β = .087, t = 2.059, p = 0.042). Patients’ self efficacy for maintaining function (SE-MF) exhibited a partner effect (β = -.768, t = 3.275, p = 0.002) on family caregivers physical health, indicating patient’s pre-operative SE-MF influenced the family caregivers health in a negative way. Conclusions: Patient’s post-operative mental health was affected by their low pre-operative tangible support. The family caregivers physical health was negatively affected by patients self efficacy for maintaining function.
Abstract 18479: Double Outlet Right Ventricle in the Adult: A Broad Spectrum of Anatomic Diagnoses and Their Association With Arrhythmia and Sudden Death
Authors: Maria Boutsikou, Alejandro Silveira-Correa, Alexander Kempny, Martin Grubler, Pawel Piatek, Rafael Alonso-Gonzalez, Lorna Swan, Anselm Uebing, Michael A Gatzoulis, Konstantinos Dimopoulos
Journal: Circulation (2016)

Background: Double outlet right ventricle (DORV) includes a broad spectrum of anatomic diagnoses, most of which amenable to biventricular repair, with a resultant improvement in survival. Limited d...
Abstract 13483: Peptide Inhibition of PTEN Improves Metabolic Recovery and Outcomes in a Murine Cardiac Arrest Model
Authors: Xiangdong Zhu, Huashan Wang, Youhua Wang, Jing Li, Alan R Leff, Terry L Vanden Hoek
Journal: Circulation (2015)

Introduction: Recent work shows that PTEN inhibition protects against cardiomyocyte contractile dysfunction and death following ischemia/reperfusion. To further determine whether PTEN inhibition improves metabolic recovery and survival in a mouse model of cardiac arrest, we have designed a TAT fused cell-permeable peptide (TAT-PTEN9c) based on the c-terminal PDZ binding motif of PTEN for rapid tissue delivery. We hypothesized that TAT-PTEN9c interferes with endogenous PTEN binding to cell membrane adaptors resulting in increased Akt activation, causing Akt-enhanced glucose utilization (with decreased diversion of glucose via the alternate polyol pathway to sorbitol) and improved survival. Methods: Mouse cardiomyocytes were isolated from 1-3 day old mouse pups. Western blot was used to identify concentrations of TAT-PTEN9c that enhanced Akt phosphorylation in mouse cardiomyocytes exposed to oxidant stress. C57BL6 mice were then subjected to an established KCL-induced 8 min cardiac arrest protocol. 30 mice after CPR were randomly assigned to receive saline or TAT-PTEN9c. MAP, ETCO2, and ECG were recorded until 4 h after successful cardiopulmonary resuscitation (CPR). TAT-PTEN9c (7.8 mg/kg) was given intravenously (IV) after CPR (n=10). As a measure of impaired glucose utilization, sorbitol content in heart and brain was determined by a fluorescence assay of NADH formation using sorbitol dehydrogenase and NAD+. Results: TAT-PTEN9c peptide enhanced Akt activation in neonatal mouse cardiomyoctes in a concentration-dependent manner. Survival was significantly increased in the TAT-PTEN9c treated group compared to saline controls at 2 h (14/15, 93% vs. 9/15, 60%, P &lt; 0.05) and 4 h (10/15, 67% vs. 6/15, 40%, P &lt; 0.05) after CPR. Treated mice had increased Akt phosphorylation within 30 min after CPR in heart and brain tissues with significantly decreased sorbitol content, suggesting improved metabolic recovery and glucose utilization. Conclusion: TAT-PTEN9c can be used after CPR in a mouse SCA model to rapidly enhance Akt activation and decrease glucose shunting via the polyol pathway in critical organs, preventing early cardiovascular collapse and death. Further work exploring the role of tissue sorbitol in sudden cardiac arrest injury is needed.
Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes
Authors: Aidin Rawshani, Araz Rawshani, Stefan Franzén, Naveed Sattar, Björn Eliasson, Ann-Marie Svensson, Björn Zethelius, Mervete Miftaraj, Darren K. McGuire, Annika Rosengren, Soffia Gudbjörnsdottir
Journal: New England Journal of Medicine (2018)

Patients with diabetes are at higher risk for death and cardiovascular outcomes than the general population. We investigated whether the excess risk of death and cardiovascular events among patients with type 2 diabetes could be reduced or eliminated.
Feasibility, Safety, and Therapeutic Efficacy of Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Sheets in a Porcine Ischemic Cardiomyopathy Model
Authors: MasashiKawamura, ShigeruMiyagawa, KenjiMiki, AtsuhiroSaito, SatsukiFukushima, TakahiroHiguchi, TakujiKawamura, ToruKuratani, TakashiDaimon, TatsuyaShimizu, TeruoOkano, YoshikiSawa
Journal: Circulation (2012)

Background—Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are a promising source of cells for regenerating myocardium. However, several issues, especially the large-scale preparation of hiPS-CMs and elimination of undifferentiated iPS cells, must be resolved before hiPS cells can be used clinically. The cell-sheet technique is one of the useful methods for transplanting large numbers of cells. We hypothesized that hiPS-CM-sheet transplantation would be feasible, safe, and therapeutically effective for the treatment of ischemic cardiomyopathy. Methods and Results—Human iPS cells were established by infecting human dermal fibroblasts with a retrovirus carrying Oct3/4, Sox2, Klf4, and c-Myc. Cardiomyogenic differentiation was induced by WNT signaling molecules, yielding hiPS-CMs that were almost 90% positive for α-actinin, Nkx2.5, and cardiac troponin T. hiPS-CM sheets were created using thermoresponsive dishes and transplanted over the myocardial infarcts in a porcine model of ischemi...
Education-dependent activation of glycolysis promotes the cytolytic potency of licensed human natural killer cells
Authors: Jolie R. Schafer, Travis C. Salzillo, Nitin Chakravarti, Meisam Naeimi Kararoudi, Prashant Trikha, Jennifer A. Foltz, Ruoning Wang, Shulin Li, Dean A. Lee
Journal: Journal of Allergy and Clinical Immunology (2018)
Robust prediction of response to immune checkpoint blockade therapy in metastatic melanoma
Authors: Noam Auslander, Gao Zhang, Joo Sang Lee, Dennie T. Frederick, Benchun Miao, Tabea Moll, Tian Tian, Zhi Wei, Sanna Madan, Ryan J. Sullivan, Genevieve Boland, Keith Flaherty, Meenhard Herlyn, Eytan Ruppin
Journal: Nature Medicine (2018)
Peroxisome Proliferator-Activated Receptor γ Activators Downregulate Angiotensin II Type 1 Receptor in Vascular Smooth Muscle Cells
Authors: KotaroTakeda, ToshihiroIchiki, TomotakeTokunou, YukoFunakoshi, NaokoIino, KatsuyaHirano, HideoKanaide, AkiraTakeshita
Journal: Circulation (2000)

Background—Peroxisome proliferator-activated receptor γ (PPARγ) activators, such as troglitazone (Tro), not only improve insulin resistance but also suppress the neointimal formation after balloon injury. However, the precise mechanisms have not been determined. Angiotensin II (Ang II) plays crucial roles in the pathogenesis of atherosclerosis, hypertension, and neointimal formation after angioplasty. We examined the effect of PPARγ activators on the expression of Ang II type 1 receptor (AT1-R) in cultured vascular smooth muscle cells (VSMCs). Methods and Results—AT1-R mRNA and AT1-R protein levels were determined by Northern blot analysis and radioligand binding assay, respectively. Natural PPARγ ligand 15-deoxy-Δ12,14-prostaglandin J2, as well as Tro, reduced the AT1-R mRNA expression and the AT1-R protein level. The PPARγ activators also reduced the calcium response of VSMCs to Ang II. PPARγ activators suppressed the AT1-R promoter activity measured by luciferase assay but did not affect the AT1-R mRNA...
Cardiac Na+-Ca2+ Exchange
Authors: MunekazuShigekawa, TakahiroIwamoto
Journal: Circulation Research (2001)

Abstract—The Na+-Ca2+ exchanger (NCX) is one of the essential regulators of Ca2+ homeostasis in cardiomyocytes and thus an important modulator of the cardiac contractile function. The purpose of this review is to survey recent advances in cardiac NCX research, with particular emphasis on molecular and pharmacological aspects. The NCX function is thought to be regulated by a variety of cellular factors. However, data obtained by use of different experimental systems often appear to be in conflict. Where possible, we endeavor to provide a rational interpretation of such data. We also provide a summary of current work relating to the structure and function of the cardiac NCX. Recent molecular studies of the NCX protein are beginning to shed light on structural features of the ion translocation pathway in the NCX membrane domain, which seems likely to be formed, at least partly, by the phylogenetically conserved α-1 and α-2 repeat structures and their neighboring membrane-spanning segments. Finally, we discus...