tbuckley/cabot-search huggingface dataset:
Prognostic Value of Quantitative Contrast-Enhanced Cardiovascular Magnetic Resonance for the Evaluation of Sudden Death Risk in Patients With Hypertrophic Cardiomyopathy
Authors: Raymond H. Chan, Barry J. Maron, Iacopo Olivotto, Michael J. Pencina, Gabriele Egidy Assenza, Tammy Haas, John R. Lesser, Christiane Gruner, Andrew M. Crean, Harry Rakowski, James E. Udelson, Ethan Rowin, Massimo Lombardi, Franco Cecchi, Benedetta Tomberli, Paolo Spirito, Francesco Formisano, Elena Biagini, Claudio Rapezzi, Carlo Nicola De Cecco, Camillo Autore, E. Francis Cook, Susie N. Hong, C. Michael Gibson, Warren J. Manning, Evan Appelbaum, Martin S. Maron
Journal: Circulation (2014)

Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden death in the young, although not all patients eligible for sudden death prevention with an implantable cardioverter-defibrillator are identified. Contrast-enhanced cardiovascular magnetic resonance with late gadolinium enhancement (LGE) has emerged as an in vivo marker of myocardial fibrosis, although its role in stratifying sudden death risk in subgroups of HCM patients remains incompletely understood.We assessed the relation between LGE and cardiovascular outcomes in 1293 HCM patients referred for cardiovascular magnetic resonance and followed up for a median of 3.3 years. Sudden cardiac death (SCD) events (including appropriate defibrillator interventions) occurred in 37 patients (3%). A continuous relationship was evident between LGE by percent left ventricular mass and SCD event risk in HCM patients (P=0.001). Extent of LGE was associated with an increased risk of SCD events (adjusted hazard ratio, 1.46/10% increase in LGE; P=0.002), even after adjustment for other relevant disease variables. LGE of ≥15% of LV mass demonstrated a 2-fold increase in SCD event risk in those patients otherwise considered to be at lower risk, with an estimated likelihood for SCD events of 6% at 5 years. Performance of the SCD event risk model was enhanced by LGE (net reclassification index, 12.9%; 95% confidence interval, 0.3-38.3). Absence of LGE was associated with lower risk for SCD events (adjusted hazard ratio, 0.39; P=0.02). Extent of LGE also predicted the development of end-stage HCM with systolic dysfunction (adjusted hazard ratio, 1.80/10% increase in LGE; P<0.03).Extensive LGE measured by quantitative contrast enhanced CMR provides additional information for assessing SCD event risk among HCM patients, particularly patients otherwise judged to be at low risk.
Drosophila, Genetic Screens, and Cardiac Function
Authors: Matthew J. Wolf, Howard A. Rockman
Journal: Circulation Research (2011)

The fruit fly, Drosophila melanogaster , has been used to study genetics, development, and signaling for nearly a century, but only over the past few decades has this tremendous resource been the focus of cardiovascular research. Fly genetics offers sophisticated transgenic systems, molecularly defined genomic deficiencies, genome-wide transgenic RNAi lines, and numerous curated mutants to perform genetic screens. As a genetically tractable model, the fly facilitates gene discovery and can complement mammalian models of disease. The circulatory system in the fly comprises well-defined sets of cardiomyocytes, and methodological advances have permitted accurate characterization of cardiac morphology and function. Thus, fly genetics and genomics offer new approaches for gene discovery of adult cardiac phenotypes to identify evolutionarily conserved molecular signals that drive cardiovascular disease.
Response of Ventilator-dependent Patients to Different Levels of Pressure Support and Proportional Assist
Authors: ELENI GIANNOULI, KIM WEBSTER, DAN ROBERTS, MAGDY YOUNES
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The ventilator's response to the patient's effort is quite different in proportional assist ventilation (PAV) and pressure support ventilation (PSV). We wished to determine whether this results in different ventilatory and breathing pattern responses to alterations in level of support and, if so, whether there are any gas exchange consequences. Fourteen patients were studied. Average elastance (E) was 22.8 (range, 14 –36) cm H2O/L and average resistance (R) was 15.7 (range, 9–21) cm H2O/L/s. The highest PSV support (PSVmax) was that associated with a tidal volume (Vt) of 10 ml/kg (20.4 ± 3.2 cm H2O), and the highest level of PAV assist (PAVmax) was 78 ± 7% of E and 76 ± 7% of R. Level of assist was decreased in steps to the lowest tolerable level (PSVmin, PAVmin). Minute ventilation, Vt, ventilator rate (RRvent), and arterial gas tensions were measured at each level. We also determined the patient's respiratory rate (RRpat) by adding the number of ineffective efforts ( Δ RR) to RRvent. There was no difference between PSVmin and PAVmin in any of the variables. At PSVmax, Vt was significantly higher (0.90 ± 0.30 versus 0.51 ± 0.16 L) and RRvent was significantly lower (13.2 ± 3.9 versus 27.6 ± 10.5 min− 1) than at PAVmax. The difference in RRvent was largely related to a progressive increase in ineffective efforts on PSV as level increased ( Δ RR 12.1 ± 10.1 vs 1.4 ± 2.1 with PAVmax); there was no significant difference in RRpat. The differences in breathing pattern had no consequence on arterial blood gas tensions. We conclude that substantial differences in breathing pattern may occur between PSV and PAV and that these are largely artifactual and related to different patient–ventilator interactions.
Evolutionary Forces Act on Promoter Length: Identification of Enriched Cis-Regulatory Elements
Authors: E. Kristiansson, M. Thorsen, M. J. Tamas, O. Nerman
Journal: Molecular Biology and Evolution (2009)

Transcription factors govern gene expression by binding to short DNA sequences called cis-regulatory elements. These sequences are typically located in promoters, which are regions of variable length upstream of the open reading frames of genes. Here, we report that promoter length and gene function are related in yeast, fungi, and plants. In particular, the promoters for stress-responsive genes are in general longer than those of other genes. Essential genes have, on the other hand, relatively short promoters. We utilize these findings in a novel method for identifying relevant cis-regulatory elements in a set of coexpressed genes. The method is shown to generate more accurate results and fewer false positives compared with other common procedures. Our results suggest that genes with complex transcriptional regulation tend to have longer promoters than genes responding to few signals. This phenomenon is present in all investigated species, indicating that evolution adjust promoter length according to gene function. Identification of cis-regulatory elements in Saccharomyces cerevisiae can be done with the web service located at http://enricher.zool.gu.se.
Hyperkinetic adult. Study of the "paradoxical" amphetamine response
Authors: L. E. Arnold
Journal: JAMA (1972)

A form of the hyperkinetic syndrome, assumed to be a juvenile condition, has been found in an adult with a previously undiagnosed condition. The pathognomonic paradoxical calming of the hyperkinetic by amphetamine was shown in a 22-year-old man and further elucidated by quantitative self-estimation of mood following doubleblind administrations of dextroamphetamine sulfate and placebo. Compared to his response to placebo, he not only showed externally visible calming and depression, but also subjectively reported decreased anxiety, increased depression, and increased concentration, with no change in self-esteem.
Cholesterol reduction and non-illness mortality: meta-analysis of randomised clinical trials
Authors: M. F Muldoon
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To investigate the association between cholesterol lowering interventions and risk of death from suicide, accident, or trauma (non-illness mortality). <b>Design:</b> Meta-analysis of the non-illness mortality outcomes of large, randomised clinical trials of cholesterol lowering treatments. <b>Studies reviewed:</b> 19 out of 21 eligible trials that had data available on non-illness mortality. <b>Interventions reviewed:</b> Dietary modification, drug treatment, or partial ileal bypass surgery for 1-10 years <b>Main outcome measure:</b> Deaths from suicides, accidents, and violence in treatment groups compared with control groups. <b>Results:</b> Across all trials, the odds ratio of non-illness mortality in the treated groups, relative to control groups, was 1.18 (95% confidence interval 0.91 to 1.52; P=0.20). The odds ratios were 1.28 (0.94 to 1.74; P=0.12) for primary prevention trials and 1.00 (0.65 to 1.55; P=0.98) for secondary prevention trials. Randomised clinical trials using statins did not show a treatment related rise in non-illness mortality (0.84, 0.50 to 1.41; P=0.50), whereas a trend toward increased deaths from suicide and violence was observed in trials of dietary interventions and non-statin drugs (1.32, 0.98 to 1.77; P=0.06). No relation was found between the magnitude of cholesterol reduction and non-illness mortality (P=0.23). <b>Conclusion:</b> Currently available evidence does not indicate that non-illness mortality is increased significantly by cholesterol lowering treatments. A modest increase may occur with dietary interventions and non-statin drugs.
WHO continues fight against SARS
Authors: A. Gonzalez Aguirre
Journal: BMJ (2003)

The World Health Organization is continuing its fight to gain control of severe acute respiratory syndrome (SARS), according to a spokesman.

Mark Slater, coordinator for WHO's SARS clinical management group, was speaking at a conference held by the UN Information Centre in London. He said that WHO was leading a worldwide effort to avoid SARS becoming another established disease in humans. He said there were still no clues about the origins of the virus and that to …
HRG Inhibits Tumor Growth and Metastasis by Inducing Macrophage Polarization and Vessel Normalization through Downregulation of PlGF
Authors: Charlotte Rolny, Massimiliano Mazzone, Sònia Tugues, Damya Laoui, Irja Johansson, Cathy Coulon, Mario Leonardo Squadrito, Inmaculada Segura, Xiujuan Li, Ellen Knevels, Sandra Costa, Stefan Vinckier, Tom Dresselaer, Peter Åkerud, Maria De Mol, Henriikka Salomäki, Mia Phillipson, Sabine Wyns, Erik Larsson, Ian Buysschaert, Johan Botling, Uwe Himmelreich, Jo A. Van Ginderachter, Michele De Palma, Mieke Dewerchin, Lena Claesson-Welsh, Peter Carmeliet
Journal: Cancer Cell (2011)
Predicting the Predisposition to Osteoporosis
Authors: Rafat Abbasi
Journal: JAMA (1986)

A reliable predictive test to identify perimenopausal women who are vulnerable to the adverse effects of severe estrogen deficiency may be useful in deciding for whom and when to begin estrogen replacement therapy. Primate models were employed to determine whether short-term treatment with gonadotropin-releasing hormone antagonist allows prospective identification of individuals at greatest risk for a negative calcium balance during overt estrogen deficiency; whether high-dose clomiphene citrate is sufficiently estrogenic to abate urinary calcium loss and to sustain vaginal and perineal tissues after ovariectomy; and whether clomiphene citrate will provide these beneficial estrogenic effects without inducing endometrial proliferation and menstruation after progestin withdrawal. The data indicate the capability of short-term gonadotropin-releasing hormone-antagonist test to identify individuals likely to lose calcium rapidly after ovariectomy. This result has potential usefulness in the prediction of susceptibility to osteoporosis after medical castration or spontaneous menopause. At high doses, clomiphene citrate therapy was nearly as effective as high-dose conjugated equine estrogens for conservation of urinary calcium, yet clomiphene citrate did not cause endometrial proliferation or withdrawal bleeding after progesterone therapy.
Development of Viral Diseases and a Viral Disease-Like Syndrome After Extracorporeal Circulation
Authors: GEORGE R. HOLSWADE, MARY ALLEN ENGLE, S. FRANK REDO, EDWARD I. GOLDSMITH, JEREMIAH A. BARONDESS
Journal: Circulation (1963)

In 170 consecutive patients with congenital or acquired cardiac disease who survived openheart operations, 14 patients (8 per cent) developed a syndrome characterized by malaise, fever, normal or low white blood count, lymphocytosis, and, in most cases, splenomegaly and hepatomegaly. The onset was usually delayed from three to six weeks after operation. Although this syndrome clinically resembled infectious mononucleosis, this diagnosis could be clearly established in only one case by heterophile antibody determinations. Nevertheless, the presence of virocytes and other similarities suggest a viral etiology for the other 13 cases.
Identification of a Novel Human Cancer/Testis Antigen, KM-HN-1, Recognized by Cellular and Humoral Immune Responses
Authors: Mikio Monji, Tetsuya Nakatsura, Satoru Senju, Yoshihiro Yoshitake, Motohiro Sawatsubashi, Masanori Shinohara, Toshiro Kageshita, Tomomichi Ono, Akira Inokuchi, Yasuharu Nishimura
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We used serologic screening of a cDNA expression library of human testis to identify novel cancer/testis antigens that elicit both humoral and cellular immune responses in cancer patients. Experimental Design and Results: We identified a novel gene designated KM-HN-1 the expression of which is testis-specific among normal tissues; it contains coiled coil domains and a leucine zipper motif and encodes a putative protein consisting of 833 amino acids. KM-HN-1 expression was observed in various cancer tissues and cancer cell lines at both mRNA and protein levels. Immunofluorescence staining of an esophageal cancer cell line revealed that KM-HN-1 protein was present exclusively in the nucleus during mitosis. Recombinant KM-HN-1 protein was produced, and used for ELISA to quantitate levels of IgG antibody specific to KM-HN-1. Higher levels of IgG antibodies specific to KM-HN-1 were detected in many types and numbers of cancer patients but not in healthy donors. The CTL lines specific to KM-HN-1, generated from HLA-A*2402–positive healthy donors and cancer patients, killed human leukocyte antigen (HLA)-A24-positive cancer cells expressing KM-HN-1 but not cell lines that did not express either KM-HN-1 or HLA-A24. Conclusions: We identified a novel cancer/testis antigen, KM-HN-1, which elicited humoral immune responses in patients with various types of cancer. Furthermore, KM-HN-1-specific CTLs could be generated from both healthy donors and cancer patients, which indicated that KM-HN-1 can be a candidate for an ideal target for cancer immunotherapy.
Oral intraepidermal IgA pustulosis and Crohn's disease
Authors: L Borradori, V Saada, M Rybojad, B Flageul, R Kuffer, M Lémann, O Verola, R Modigliani, P Morel
Journal: British Journal of Dermatology (1992)

A case is reported of a 60-year-old woman with Crohn's disease who developed recurrent oral blisters and erosions. The histopathology of the buccal mucosa showed intraepidermal bullae and clefts with an intense accumulation of neutrophils in the epithelium. Direct immunofluorescence revealed intercellular IgA predominantly in the basal and suprabasal layers and in one biopsy concurrent deposits of IgG. No circulating autoantibodies were detected.
<i>I</i> <sub>f</sub> Current and Spontaneous Activity in Mouse Embryonic Ventricular Myocytes
Authors: Kenji Yasui, Weiran Liu, Tobias Opthof, Kenji Kada, Jong-Kook Lee, Kaichiro Kamiya, Itsuo Kodama
Journal: Circulation Research (2001)

Knowledge of the initiation of electrical and contractile activity in the embryonic heart relies to a large extent on data obtained in chicken. In recent years, molecular biological techniques have raised an interest in mouse physiology, including early embryonic development. We studied action potentials and the occurrence of one of the pacemaker currents, I(f), by the whole-cell voltage and current-clamp technique at the earliest stage at which a regular heartbeat is established (9.5 days postcoitum) and at 1 day before birth. We show, first, that at the early stage there is a prominent I(f) in mouse embryonic ventricles, which decreases by 82% before birth in concert with the loss of regular spontaneous activity of ventricular cells. Second, the decrease in I(f) current is associated with a slight change in channel gating kinetics and a decrease in total mRNA expression of the genes encoding for I(f) current. Third, the most prevalent mRNA subtype is switched from HCN4 to HCN2 during the second half of embryonic development. Fourth, the I(f) current may be modulated by the beta-adrenergic cascade, although the coupling to the beta-adrenoceptor in the sarcolemma itself is not yet mature. We conclude that I(f) current of the sinus node type is present in early embryonic mouse ventricular cells. In association with a loss of I(f) current, the ventricle tends to lose pacemaker potency during the second half of embryonic development.
Attachment and Traumatic Stress in Female Holocaust Child Survivors and Their Daughters
Authors: Abraham Sagi-Schwartz, Marinus H Van IJzendoorn, Klaus E Grossmann, Tirtsa Joels, Karin Grossmann, Miri Scharf, Nina Koren-Karie, Sarit Alkalay
Journal: American Journal of Psychiatry (2003)

During the Holocaust, extreme trauma was inflicted on children who experienced it. Two questions were central to the current investigation. First, do survivors of the Holocaust still show marks of their traumatic experiences, even after more than 50 years? Second, was the trauma passed on to the next generation?Careful matching of Holocaust survivors and comparison subjects was employed to form a research study design with three generations, including 98 families with a grandmother, a mother, and an infant, who engaged in attachment- and trauma-related interviews, questionnaires, and observational procedures.Holocaust survivors (now grandmothers) showed more signs of traumatic stress and more often lack of resolution of trauma than comparison subjects, but they were not impaired in general adaptation. Also, the traumatic effects did not appear to transmit across generations.Holocaust survivors may have been able to protect their daughters from their war experiences, although they themselves still suffer from the effects of the Holocaust.
Melamine Toxicity and the Kidney
Authors: Anthony Kai-ching Hau, Tze Hoi Kwan, Philip Kam-tao Li
Journal: Journal of the American Society of Nephrology (2009)

The toxicity of melamine caught the attention of physicians as a result of a recent spate of renal injury after exposure to melamine-tainted milk in China. Melamine is an organic nitrogenous compound used in the production of plastics, dyes, fertilizers, and fabrics. In the current incident, melamine was added to milk to elevate falsely assay results for protein content. A variety of toxic effects from melamine, including nephrolithiasis, chronic kidney inflammation, and bladder carcinoma, all have been studied in animals. We review here the epidemiology, clinical features, and investigative findings concerning the only outbreak of melamine poisoning in humans. We also examine the renal toxicities of melamine and cyanuric acid—a by-product of its synthesis—and the associated risk factors on exposure and provide guidance on levels in foods.
Type I human T cell leukemia virus tax protein transforms rat fibroblasts through the cyclic adenosine monophosphate response element binding protein/activating transcription factor pathway.
Authors: M R Smith, W C Greene
Journal: Journal of Clinical Investigation (1991)

The Tax oncoprotein of the type I human T cell leukemia virus (HTLV-I) activates transcription of cellular and viral genes through at least two different transcription factor pathways. Tax activates transcription of the c-fos proto-oncogene by a mechanism that appears to involve members of the cAMP response element binding protein (CREB) and activating transcription factor (ATF) family of DNA-binding proteins. Tax also induces the nuclear expression of the NF-kappa B family of rel oncogene-related enhancer-binding proteins. We have investigated the potential role of these CREB/ATF and NF-kappa B/Rel transcription factors in Tax-mediated transformation by analyzing the oncogenic potential of Tax mutants that functionally segregate these two pathways of transactivation. Rat fibroblasts (Rat2) stably expressing either the wild-type Tax protein or a Tax mutant selectively deficient in the ability to induce NF-kappa B/Rel demonstrated marked changes in morphology and growth characteristics including the ability to form tumors in athymic mice. In contrast, Rat2 cells stably expressing a Tax mutant selectively deficient in the ability to activate transcription through CREB/ATF demonstrated no detectable changes in morphology or growth characteristics. These results suggest that transcriptional activation through the CREB/ATF pathway may play an important role in Tax-mediated cellular transformation.
All approved US embryonic stem cell lines may be contaminated
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

The few stem cell lines approved in the United States are probably contaminated with a non-human molecule, says a study published online ahead of print publication in Nature Medicine (www.nature.com/nm/). The researchers recommend starting afresh with human embryonic stem cells that have never been exposed to animal products.

The authors, researchers at the University of California at San Diego and the Salk Institute in La Jolla, California, report that the human embryonic stem cells they studied are contaminated with non-human sialic acid that could cause rejection if the stem cells were transplanted into humans. “In …
GGAP2/PIKE-A Directly Activates Both the Akt and Nuclear Factor-κB Pathways and Promotes Prostate Cancer Progression
Authors: Yi Cai, Jianghua Wang, Rile Li, Gustavo Ayala, Michael Ittmann, Mingyao Liu
Journal: Cancer Research (2009)

GGAP2/PIKE-A is a GTP-binding protein that can enhance Akt activity. Increased activation of the AKT and nuclear factor-kappaB (NF-kappaB) pathways have been identified as critical steps in cancer initiation and progression in a variety of human cancers. We have found significantly increased expression GGAP2 in the majority of human prostate cancers and GGAP2 expression increases Akt activation in prostate cancer cells. Thus, increased GGAP2 expression is a common mechanism for enhancing the activity of the Akt pathway in prostate cancers. In addition, we have found that activated Akt can bind and phosphorylate GGAP2 at serine 629, which enhances GTP binding by GGAP2. Phosphorylated GGAP2 can bind the p50 subunit of NF-kappaB and enhances NF-kappaB transcriptional activity. When expressed in prostate cancer cells, GGAP2 enhances proliferation, foci formation, and tumor progression in vivo. Thus, increased GGAP2 expression, which is present in three quarters of human prostate cancers, can activate two critical pathways that have been linked to prostate cancer initiation and progression.