tbuckley/cabot-search huggingface dataset:
Polycomb Repressive Complex 2 Regulates Normal Development of the Mouse Heart
Authors: Aibin He, Qing Ma, Jingjing Cao, Alexander von Gise, Pingzhu Zhou, Huafeng Xie, Bing Zhang, Michael Hsing, Danos C. Christodoulou, Patrick Cahan, George Q. Daley, Sek Won Kong, Stuart H. Orkin, Christine E. Seidman, Jonathan G. Seidman, William T. Pu
Journal: Circulation Research (2011)

Rationale: Epigenetic marks are crucial for organogenesis, but their role in heart development is poorly understood. Polycomb repressive complex 2 (PRC2) trimethylates histone H3 at lysine 27, which establishes H3K27me3 repressive epigenetic marks that promote tissue-specific differentiation by silencing ectopic gene programs. Objective: We studied the function of PRC2 in murine heart development using a tissue-restricted conditional inactivation strategy. Methods and Results: Inactivation of the PRC2 subunit Ezh2 by Nkx2–5 Cre (Ezh2 NK ) caused lethal congenital heart malformations, namely, compact myocardial hypoplasia, hypertrabeculation, and ventricular septal defect. Candidate and genome-wide RNA expression profiling and chromatin immunoprecipitation analyses of Ezh2 NK heart identified genes directly repressed by EZH2. Among these were the potent cell cycle inhibitors Ink4a/b (inhibitors of cyclin-dependent kinase 4 A and B), the upregulation of which was associated with decreased cardiomyocyte proliferation in Ezh2 NK . EZH2-repressed genes were enriched for transcriptional regulators of noncardiomyocyte expression programs such as Pax6 , Isl1 , and Six1 . EZH2 was also required for proper spatiotemporal regulation of cardiac gene expression, because Hcn4 , Mlc2a , and Bmp10 were inappropriately upregulated in ventricular RNA. PRC2 was also required later in heart development, as indicated by cardiomyocyte-restricted TNT-Cre inactivation of the PRC2 subunit Eed . However, Ezh2 inactivation by TNT-Cre did not cause an overt phenotype, likely because of functional redundancy with Ezh1 . Thus, early Ezh2 inactivation by Nk2–5 Cre caused later disruption of cardiomyocyte gene expression and heart development. Conclusions: Our study reveals a previously undescribed role of EZH2 in regulating heart formation and shows that perturbation of the epigenetic landscape early in cardiogenesis has sustained disruptive effects at later developmental stages.
Disposing of the undisposable.
Authors: C L Hewer
Journal: BMJ (1971)

describe four patients who developed acute myeloblastic leukaemia after treatment of a hypoplastic anaemia with oxymetholone.I should like to report a similar case.A 51-year-old man presented in April 1969.The blood count was: haemoglobin 9-4 g/100 ml, white cells 2,800/mm3 (neutrophils 44%0/, lymphocytes 500), plate- lets 58,000, and reticulocytes 0-8 %.The marrow aspirate was markedly hypoplastic, and there were no atypical cells.A trans- fusion was given but in July a similar blood count was found and treatment was there- after with oxymetholone 5 mg thrice daily and prednisone continuously, together with frequent blood transfusions.The total dosage of oxymetholone over the next 2 years was no more than 11 g.In July 1971 a rapid deterioration in the patient's health was observed and myelo- blasts appeared in the peripheral blood.
Single Ventricle Reconstruction Trial
Authors: David N. Rosenthal
Journal: Circulation (2014)

H ypoplastic left heart syndrome, which occurs in 1 per 5000 live births, refers to a family of cardiac defects that are characterized by hypoplasia of the structures making up the left side of the circulation, including the mitral and aortic valves, the left atrium and left ventricle, and the aorta.Infants with this syndrome typically undergo a 3-stage surgical palliation.Without this surgery, the defect is lethal.Since the report of the first Norwood procedure 1 for hypoplastic left heart syndrome by Dr William Norwood in 1981, results from treatment of hypoplastic left heart syndrome have improved considerably.In a large single-center report, operative mortality associated with the first-stage procedure was reduced from 59% to 19% between 1990 and 2001. 2 Nonetheless, the complete palliative sequence entails 3 surgeries and has considerable interstage mortality, so the overall survival for patients with hypoplastic left heart syndrome remains poor.
Independent differentiative pathways of Ly1 and Ly23 subclasses of T cells. Experimental production of mice deprived of selected T-cell subclasses.
Authors: B Huber, H Cantor, F W Shen, E A Boyse
Journal: The Journal of Experimental Medicine (1976)

When B mice are supplied with Ly1 or Ly23 cells they acquire, over the next 6 mo, only the immune functions associated with each of these T-cell subclasses, respectively. The T-cell population of these "B-Ly1" and "B-Ly23" mice mice also remains restricted to the Ly1 and Ly23 subclass phenotypes. Thus the Ly1 and Ly23 populations are derived from two separate lines of differentiation and are not sequential stages of a single differentiative pathway.
CD31 expressed on distinctive T cell subsets is a preferential amplifier of beta 1 integrin-mediated adhesion.
Authors: Y Tanaka, S M Albelda, K J Horgan, G A van Seventer, Y Shimizu, W Newman, J Hallam, P J Newman, C A Buck, S Shaw
Journal: The Journal of Experimental Medicine (1992)

The CD31 (platelet endothelial cell adhesion molecule-1 [PECAM-1]/endothelial cell adhesion molecule [endoCAM]) molecule expressed on leukocytes, platelets, and endothelial cells is postulated to mediate adhesion to endothelial cells and thereby function in immunity, inflammation, and wound healing. We report the following novel features of CD31 which suggests a role for it in adhesion amplification of unique T cell subsets: (a) engagement of CD31 induces the adhesive function of beta 1 and beta 2 integrins; (b) adhesion induction by CD31 immunoglobulin G (IgG) monoclonal antibodies (mAbs) is sensitive, requiring only bivalent mAb; (c) CD31 mAb induces adhesion rapidly, but it is transient; (d) unique subsets of CD4+ and CD8+ T cells express CD31, including all naive (CD45RA+) CD8 T cells; and (e) CD31 induction is selective, inducing adhesive function of beta 1 integrins, particularly very late antigen-4, more efficiently than the beta 2 integrin lymphocyte function-associated antigen-1. Conversely, CD3 is more effective in inducing beta 2-mediated adhesion. Taken together, these findings indicate that unique T cell subsets express CD31, and CD31 has the capacity to induce integrin-mediated adhesion of T cells in a sensitive and selective fashion. We propose that, in collaboration with other receptors/ligands, CD31 functions in an "adhesion cascade" by amplifying integrin-mediated adhesion of CD31+ T cells to other cells, particularly endothelial cells.
Highly Efficient Hierarchical Micelles Integrating Photothermal Therapy and Singlet Oxygen-Synergized Chemotherapy for Cancer Eradication
Authors: Zhihui Wan, Huajian Mao, Miao Guo, Yanli Li, Aijun Zhu, Hong Yang, Hui He, Junkang Shen, Lijuan Zhou, Zhen Jiang, Cuicui Ge, Xiaoyuan Chen, Xiangliang Yang, Gang Liu, Huabing Chen
Journal: Theranostics (2014)

It is highly desirable to develop theranostic nanoparticles for achieving cancer imaging with enhanced contrast and simultaneously multimodal synergistic therapy.Herein, we report a theranostic micelle system hierarchically assembling cyanine dye (indocyanine green) and chemotherapeutic compound (doxorubicin) (I/D-Micelles) as a novel theranostic platform with high drug loading, good stability and enhanced cellular uptake via clathrin-mediated endocytosis.I/D-Micelles exhibit the multiple functionalities including near-infrared fluorescence (NIRF), hyperthermia and intracellular singlet oxygen from indocyanine green, and simultaneous cytotoxicity from doxorubicin.Upon photoirradiation, I/D-Micelles can induce NIRF imaging, acute photothermal therapy via hyperthermia and simultaneous synergistic chemotherapy via singlet oxygen-triggered disruption of lysosomal membranes, eventually leading to enhanced NIRF imaging and superior tumor eradication without any re-growth.Our results suggest that the hierarchical micelles can act as a superior theranostic platform for cancer imaging and multimodal synergistic therapy.
α <sub>1</sub> -Adrenergic Activation Inhibits β-Adrenergic–Stimulated Unitary Ca <sup>2+</sup> Currents in Cardiac Ventricular Myocytes
Authors: Long Chen, Nabil El-Sherif, Mohamed Boutjdir
Journal: Circulation Research (1996)

We have previously shown that whole-cell L-type Ca 2+ current that was stimulated through β-adrenergic receptors was negatively modulated by α 1 -adrenergic activation. In the present study, we investigated the kinetic basis of this modulation at the single-channel level in adult rat ventricular myocytes using Ba 2+ as the charge carrier. Unitary current sweeps were evoked by 300-ms depolarizing pulses to 0 mV, from a holding potential of −50 mV at 0.5 Hz. During control conditions, the ensemble-averaged current amplitude was 0.18±0.01 pA (n=7). To achieve β-adrenergic stimulation (β effect), cells were superfused with norepinephrine (10 μmol/L) in the presence of prazosin (10 μmol/L), an α 1 -adrenergic blocker. β-Adrenergic stimulation enhanced ensemble-averaged current (from 0.18±0.01 to 0.75±0.04 pA, P &lt;.05, n=7), increased the open-time constants, and decreased the closed-time constants. To activate α 1 -receptors while maintaining the β-adrenergic stimulation, cells were superfused with norepinephrine alone (α 1 +β effects). α 1 -Adrenergic activation reduced ensemble-averaged current (from 0.75±0.04 to 0.41±0.03 pA, P &lt;.05, n=7), decreased open-time constants, and increased closed-time constants. α 1 -Adrenergic activation also inhibited ensemble-averaged currents stimulated by a low concentration (10 μmol/L) of 8-bromo-cAMP but not by (−)Bay K 8644 (1 μmol/L). Calphostin C (1 μmol/L), a specific inhibitor of protein kinase C, attenuated α 1 -adrenergic inhibition on β-adrenergic–stimulated unitary currents. We conclude that α 1 -adrenergic activation exerts an inhibitory effect on β-adrenergic–stimulated unitary Ba 2+ current at the single-channel level. The shortening of the open-time and the lengthening of the closed-time constants and the increase in blank sweeps may explain the inhibition of the Ca 2+ -channel activity and the reduction in whole-cell Ca 2+ current previously reported. This inhibition is in part mediated through the protein kinase C pathway.
Follicular thyroid cells of autoimmune thyroiditis may coexpress ICAM-1 (CD54) and its natural ligand LFA-1 (CD11a/CD18)
Authors: M BAGNASCO, G PESCE, A CARETTO, F PAOLIERI, C PRONZATO, B VILLAGGIO, C GIORDANO, C BETTERLE, G CANONICA
Journal: Journal of Allergy and Clinical Immunology (1995)
Ca++ distribution after Na+ pump inhibition in cultured neonatal rat myocardial cells.
Authors: J M Burt, G A Langer
Journal: Circulation Research (1982)

The influence of inhibition of the Na+ pump, with secondary stimulation of Na+-Ca++ exchange, on cellular Ca++ distribution is examined using the on-line scintillation disk technique and cultured neonatal rat myocardial cells. Under control conditions, La+++ displaced 78.1 +/- 1.13% (SEM) of the total cell associated 45Ca. Application of 1 mm ouabain or reduction of [K+]o to 0.5 mM resulted in a net increase of 10.6 +/- 1.3% and 13.8 +/- 2%, respectively, in total cell-associated Ca++. Of this added 45Ca, 75.9 +/- 2.7% and 78.4 +/- 2.1%, respectively remained La+++-displaceable. The 45Ca-binding characteristics of isolated sarcolemma, prepared from the cultured neonatal rat myocardial cells using the gas dissection technique, were examined. When treated with either ouabain or low [K+]o solutions, sarcolemmal 45Ca binding did not change. This result indicates that functional, intact tissue is necessary to observe the Ca++ increase. Treatment of the cells with verapamil before and during ouabain exposure failed to inhibit the ouabain-induced increase in cell-associated 45Ca. The evidence indicates that inhibition of the Na+-pump, and secondary stimulation of Na+-Ca++ exchange, result in a net increase of 11-15% in cell-associated Ca++, 78% of which remains La+++-displaceable and is, therefore, localized to the sarcolemma-glycocalyx complex.
THE USE OF COMIC CARTOONS FOR THE STUDY OF SOCIAL COMPREHENSION IN SCHIZOPHRENIA
Authors: RITA SENF, PAUL E. HUSTON, BERTRAM D. COHEN
Journal: American Journal of Psychiatry (1956)

A method of analyzing responses to comic cartoons is presented as a means of studying social comprehension. The method was applied to 4 groups of patients: chronic schizophrenic, early schizophrenic, depressive, and neurotic. No group showed impairment in simple description of the environment depicted in the cartoons. Proceeding through the categories of Speakers, Action, Social Roles, Motivation, and Humor, decreasing adequacy of response was apparent for all groups. The CS group showed impairment in all these categories relative to the other 3 groups. For the ES patients there was a suggestion of deficit in Action, Motivation, and Humor; but these patients were clearly better than the CS group. The Dp and Nt groups did not differ from each other. The schizophrenic patient has difficulty in understanding social interactions, even in the simple situations depicted in the cartoons used here. Since the ES patients tended to have difficulty in the more complex categories, it is suggested that the ability to interpret these more complex aspects of interpersonal situations is impaired early in the course of schizophrenia. This method helps to clarify the nature of the schizophrenic difficulty in social interactions. Further development of the method may permit greater clarification of the psychopathology of interpersonal relations in various diagnostic groups.
Hedgehog signaling regulates FOXA2 in esophageal embryogenesis and Barrett’s metaplasia
Authors: David H. Wang, Anjana Tiwari, Monica E. Kim, Nicholas J. Clemons, Nanda L. Regmi, William A. Hodges, David M. Berman, Elizabeth A. Montgomery, D. Neil Watkins, Xi Zhang, Qiuyang Zhang, Chunfa Jie, Stuart J. Spechler, Rhonda F. Souza
Journal: Journal of Clinical Investigation (2014)

Metaplasia can result when injury reactivates latent developmental signaling pathways that determine cell phenotype. Barrett's esophagus is a squamous-to-columnar epithelial metaplasia caused by reflux esophagitis. Hedgehog (Hh) signaling is active in columnar-lined, embryonic esophagus and inactive in squamous-lined, adult esophagus. We showed previously that Hh signaling is reactivated in Barrett's metaplasia and overexpression of Sonic hedgehog (SHH) in mouse esophageal squamous epithelium leads to a columnar phenotype. Here, our objective was to identify Hh target genes involved in Barrett's pathogenesis. By microarray analysis, we found that the transcription factor Foxa2 is more highly expressed in murine embryonic esophagus compared with postnatal esophagus. Conditional activation of Shh in mouse esophageal epithelium induced FOXA2, while FOXA2 expression was reduced in Shh knockout embryos, establishing Foxa2 as an esophageal Hh target gene. Evaluation of patient samples revealed FOXA2 expression in Barrett's metaplasia, dysplasia, and adenocarcinoma but not in esophageal squamous epithelium or squamous cell carcinoma. In esophageal squamous cell lines, Hh signaling upregulated FOXA2, which induced expression of MUC2, an intestinal mucin found in Barrett's esophagus, and the MUC2-processing protein AGR2. Together, these data indicate that Hh signaling induces expression of genes that determine an intestinal phenotype in esophageal squamous epithelial cells and may contribute to the development of Barrett's metaplasia.
Does the form of akinetic mutism linked to mesodiencephalic injuries bridge the double dissociation of Parkinson's disease and catatonia?
Authors: Ayeesha K. Kamal, Nicholas D. Schiff
Journal: Behavioral and Brain Sciences (2002)

Northoff provides a compelling argument supporting a kind of “double dissociation” of Parkinson's disease and catatonia. We discuss a related form of akinetic mutism linked to mesodiencephalic injuries and suggest an alternative to the proposed “horizontal” versus “vertical” modulation distinction. Rather than a “directional” difference in patterned neuronal activity, we propose that both disorders reflect hypersynchrony within typically interdependent but segregated networks facilitated by a common thalamic gating mechanism.
Prevalence of Major Cardiovascular Risk Factors and Cardiovascular Diseases Among Hispanic/Latino Individuals of Diverse Backgrounds in the United States
Authors: Martha L. Daviglus, Gregory A. Talavera, M. Larissa Avilés-Santa, Matthew Allison, Jianwen Cai, Michael H. Criqui, Marc Gellman, Aida L. Giachello, Natalia Gouskova, Robert C. Kaplan, Lisa LaVange, Frank Penedo, Krista Perreira, Amber Pirzada, Neil Schneiderman, Sylvia Wassertheil-Smoller, Paul D. Sorlie, Jeremiah Stamler
Journal: JAMA (2012)

Major cardiovascular diseases (CVDs) are leading causes of mortality among US Hispanic and Latino individuals. Comprehensive data are limited regarding the prevalence of CVD risk factors in this population and relations of these traits to socioeconomic status (SES) and acculturation.To describe prevalence of major CVD risk factors and CVD (coronary heart disease [CHD] and stroke) among US Hispanic/Latino individuals of different backgrounds, examine relationships of SES and acculturation with CVD risk profiles and CVD, and assess cross-sectional associations of CVD risk factors with CVD.Multicenter, prospective, population-based Hispanic Community Health Study/Study of Latinos including individuals of Cuban (n = 2201), Dominican (n = 1400), Mexican (n = 6232), Puerto Rican (n = 2590), Central American (n = 1634), and South American backgrounds (n = 1022) aged 18 to 74 years. Analyses involved 15,079 participants with complete data enrolled between March 2008 and June 2011.Adverse CVD risk factors defined using national guidelines for hypercholesterolemia, hypertension, obesity, diabetes, and smoking. Prevalence of CHD and stroke were ascertained from self-reported data.Age-standardized prevalence of CVD risk factors varied by Hispanic/Latino background; obesity and current smoking rates were highest among Puerto Rican participants (for men, 40.9% and 34.7%; for women, 51.4% and 31.7%, respectively); hypercholesterolemia prevalence was highest among Central American men (54.9%) and Puerto Rican women (41.0%). Large proportions of participants (80% of men, 71% of women) had at least 1 risk factor. Age- and sex-adjusted prevalence of 3 or more risk factors was highest in Puerto Rican participants (25.0%) and significantly higher (P < .001) among participants with less education (16.1%), those who were US-born (18.5%), those who had lived in the United States 10 years or longer (15.7%), and those who preferred English (17.9%). Overall, self-reported CHD and stroke prevalence were low (4.2% and 2.0% in men; 2.4% and 1.2% in women, respectively). In multivariate-adjusted models, hypertension and smoking were directly associated with CHD in both sexes as were hypercholesterolemia and obesity in women and diabetes in men (odds ratios [ORs], 1.5-2.2). For stroke, associations were positive with hypertension in both sexes, diabetes in men, and smoking in women (ORs, 1.7-2.6).Among US Hispanic/Latino adults of diverse backgrounds, a sizeable proportion of men and women had adverse major risk factors; prevalence of adverse CVD risk profiles was higher among participants with Puerto Rican background, lower SES, and higher levels of acculturation.
Shame and Implicit Self-Concept in Women With Borderline Personality Disorder
Authors: Nicolas Rüsch, Klaus Lieb, Ines Göttler, Christiane Hermann, Elisabeth Schramm, Harald Richter, Gitta A Jacob, Patrick W Corrigan, Martin Bohus
Journal: American Journal of Psychiatry (2007)

Shame is considered to be a central emotion in borderline personality disorder and to be related to self-injurious behavior, chronic suicidality, and anger-hostility. However, its level and impact on people with borderline personality disorder are largely unknown. The authors examined levels of self-reported shame, guilt, anxiety, and implicit shame-related self-concept in women with borderline personality disorder and assessed the association of shame with self-esteem, quality of life, and anger-hostility.Sixty women with borderline personality disorder completed self-report measures of shame- and guilt-proneness, state shame, anxiety, depression, self-esteem, quality of life, and clinical symptoms. Comparison groups consisted of 30 women with social phobia and 60 healthy women. Implicit shame-related self-concept (relative to anxiety) was assessed by the Implicit Association Test.Women with borderline personality disorder reported higher levels of shame- and guilt-proneness, state shame, and anxiety than women with social phobia and healthy comparison subjects. The implicit self-concept in women with borderline personality disorder was more shame-prone (relative to anxiety-prone) than in women in the comparison groups. After depression was controlled for, shame-proneness was negatively correlated with self-esteem and quality of life and positively correlated with anger-hostility.Shame, an emotion that is prominent in women with borderline personality disorder, is associated with the implicit self-concept as well as with poorer quality of life and self-esteem and greater anger-hostility. Psychotherapeutic approaches to borderline personality disorder need to address explicit and implicit aspects of shame.
A simple prognostic scoring system for patients receiving transarterial embolisation for hepatocellular cancer
Authors: L. Kadalayil, R. Benini, L. Pallan, J. O'Beirne, L. Marelli, D. Yu, A. Hackshaw, R. Fox, P. Johnson, A.K. Burroughs, D.H. Palmer, T. Meyer
Journal: Annals of Oncology (2013)

BackgroundThe prognosis for patients with hepatocellular cancer (HCC) undergoing transarterial therapy (TACE/TAE) is variable.MethodsWe carried out Cox regression analysis of prognostic factors using a training dataset of 114 patients treated with TACE/TAE. A simple prognostic score (PS) was developed, validated using an independent dataset of 167 patients and compared with Child–Pugh, CLIP, Okuda, Barcelona Clinic Liver Cancer (BCLC) and MELD.ResultsLow albumin, high bilirubin or α-fetoprotein (AFP) and large tumour size were associated with a two- to threefold increase in the risk of death. Patients were assigned one point if albumin <36 g/dl, bilirubin >17 μmol/l, AFP >400 ng/ml or size of dominant tumour >7 cm. The Hepatoma arterial-embolisation prognostic (HAP) score was calculated by summing these points. Patients were divided into four risk groups based on their HAP scores; HAP A, B, C and D (scores 0, 1, 2 and >2, respectively). The median survival for the groups A, B, C and D was 27.6, 18.5, 9.0 and 3.6 months, respectively. The HAP score validated well with the independent dataset and performed better than other scoring systems in differentiating high- and low-risk groups.ConclusionsThe HAP score predicts outcomes in patients with HCC undergoing TACE/TAE and may help guide treatment selection, allow stratification in clinical trials and facilitate meaningful comparisons across reported series.