tbuckley/cabot-search huggingface dataset:
Abstract 14089: Apelin Enhances Myocardial Glucose Uptake Through Activation of AMPK and Gq Signaling
Authors: Shiming Xu, Philip S Tsao, Mei Huang, Joseph C Wu, Patrick Yue
Journal: Circulation (2011)

Background: Apelin is a ubiquitously expressed endogenous peptide hormone recently shown to increase systemic insulin sensitivity. However, little is known about its effects on cardiac glucose upta...
Delayed Mortality of Radiation Chimeras: A Pathological and Hematological Study
Authors: M.J. de Vries, O. Vos
Journal: JNCI Journal of the National Cancer Institute (1959)

The hematological and pathological changes in lethally X-irradiated mice treated with isologous, homologous, or heterologous (rat) bone marrow are reported. Two different disease entities were observed in mice treated with homologous or heterologous bone marrow. Bone marrow aplasia chiefly occurred before the 30th day after irradiation. This resulted in death from septicemia or hemorrhage. The secondary bone marrow failure is explained by an immunological reaction of the host against the bone marrow graft. After the 30th postirradiation day, the animals were emaciated and had dermatitis, pneumonia, diarrhea caused by focal colitis with crypt degeneration, and necrosis of the liver. The delayed foreign bone marrow reaction is of a complex nature. Impaired recovery of radiation-induced lesions, decreased resistance to bacterial infections, probably due to generalized atrophy of the lymphatic tissues, as well as an immunological reaction of the graft against the host are postulated to be causal factors. An important difference was noted between animals treated with heterologous and those treated with homologous bone marrow. Bone marrow aplasia pre-dominated in the mice of the former group. In contrast, the mice of the latter group were chiefly affected by pneumonia, diarrhea, and colitis. Regeneration of the lymphatic tissues occurred within a month after irradiation in animals treated with isologous bone marrow, but it was retarded or failed to occur in animals treated with foreign bone marrow. The possible relation of the lymphatic-tissue changes to the etiology of the “secondary disease” is discussed.
P0188 : Hepatopulmonary syndrome. Prevalence, associated factors and impact in survival after liver transplantation
Authors: E. Dueñas, R. Rota, J. Ribas, A. Ruiz-Mayoral, M.E. González, A. Amador, C. Baliellas, J. Fabregat, X. Xiol, J. Castellote
Journal: Journal of Hepatology (2015)
Abstract 16074: The Role of Nuclear Nox4 in Mediating Oxidation of HDAC4 in Response to Phenylephrine Stimulation
Authors: Shoji Matsushima, Junya Kuroda, Tetsuro Ago, Junichi Sadoshima
Journal: Circulation (2011)

INTRODUCTION: Reduction and oxidation are critically involved in the pathogenesis of cardiac hypertrophy and heart failure. Oxidation of conserved cysteine residues in histone deacetylase 4 (HDAC4)...
Telomeric G-tail is a new target for cancer therapy
Authors: Hidetoshi Tahara, Toshinori Ide
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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Telomere is a special structure at the end of chromosomes. Most telomere DNA is composed of double stranded DNA, but very ends of telomere DNA have single-stranded, 3’-overhang of between 50 and 400 bases in the G-rich strand, the so-called G-tail. The G-tail length is essential for formation of t-loop and chromosome maintenance. Dominant negative telomere binding protein TRF2 induces the dissociation of TRF2 binding from telomeres and the destruction of G-tail accompanied by G-tail shortening. G-tail length reduction also observed in in vitro cellular senescence. Recently, we have developed G-tail telomere HPA, a new technique to measure telomeric G-tail (Nature Methods, 2005). This method has the advantage of being simple to perform, accurate and highly sensitive for G-tail as short as 20 nucleotides. In addition, this assay is specific and quantitative for G-tail, and can be used for large-scale screening to understanding diseases associated with ageing and telomere dysfunction. Using this assay, we have measured G-tail length in cancer and normal cells treated with telomestatin, G-quadruplex stabilizing telomerase inhibitor. Interestingly, telomestatin induced rapid cell death accompanied with G-tail reduction in cancer cells, but not in normal cells. Binding of telomere binding protein TRF2 to telomere in telomestatin treated cells was examined by telomere ChIP assay. About 90 % of TRF2 was dissociated from telomere whereas TRF1 dissociation was 10%. The rate of TRF2 dissociation from telomere was well correlated with the rate of anaphase bridge formation and G-tail reduction. These results indicated that G-tail destruction compounds should be new type of powerful anti-cancer drugs, and G-tail telomere HPA have practical benefits for screening of G-tail targeted anti-cancer drugs.
Child labour
Authors: T. J Scanlon
Journal: BMJ (2002)

Child labour today represents the largest single cause of child abuse across the globe. Most of it takes place in economically less developed countries, and much is hidden. In a minority of instances the effects of child labour may be neutral or even positive, such as helping out in a family run shop during school holidays. In recent years therefore the emphasis has shifted from the abolition of all forms of child labour to the elimination of intolerable and hazardous child labour. The International Labour Organisation estimates that worldwide 110 million children aged 5-14 years are engaged in labour that can be described as hazardous or intolerable.1 Most of this takes place in Asia and the Pacific, although the highest prevalence is in Africa, where children younger than 14 years make up a third of the total workforce.1

Slavery, bonded labour, prostitution, and the recruitment of child soldiers are all intolerable and illegal. Yet in central and west Africa alone an estimated 200 000 children are traded each year.2 Landlords can bond a child worker for as little as US$1.50 (£0.95, €1.50), and family debts are manipulated so that there is no hope of repayment. The commercial sexual exploitation of children is increasing, and organised networks can be found in Latin America, Asia, Africa, and, most recently, eastern Europe. An estimated 1 million children in Asia alone are victims of the sex trade, much of it focused around sex tourism.3 Paradoxically, …
Abstract 5311: Proteolysis-resistant Collagen Drives Vascular Smooth Muscle Cell Senescence
Authors: Faran Vafaie, Caroline O’Neil, Alanna Watson, David Holdsworth, J. Geoffrey Pickering
Journal: Circulation (2009)

Senescence of vascular smooth muscle cells (SMCs) has recently been identified as a feature of atherosclerosis. However, the factors that lead to premature SMC senescence are not well understood. Plaque SMCs reside within a milieu of type I collagen fibrils that, over time, can undergo progressive intermolecular cross-linking rendering the collagen resistant to proteol-ysis. We hypothesized that vascular SMC longevity depends on the extent to which the surrounding type I collagen can be proteolytically edited. To test this, we studied mice with a targeted mutation of the 3/4 −1/4 collagenase cleavage site in type I collagen (Col1a1r/r). Mice harboring the Col1a1r/r mutation appeared normal up to 5 months of age but subsequently developed features of premature aging, including shortened lifespan (p&lt;0.01), impaired weight gain (p&lt;0.01), decreased adipose tissue content (p&lt;0.01), and increased kyphosis (p&lt;0.05), the latter two attributes quantified by micro CT imaging. Furthermore, SMCs in the aortic wall of aged, Col1a1r/r mice showed increased accumulation of reactive oxygen species, as assessed by hydroethidine incubation and nuclear fluorescence. To determine if collagenase-resistant collagen directly impacted SMC lifespan, primary human SMCs were cultured on collagen harvested from the tails of wild-type or Col1a1r/r mice. SMCs on mutant collagen displayed a 67% decrease in cumulative population doublings (p&lt;0.01), which was associated with increased senescence-associated beta-galactosidase (SA-β-gal) activity (p&lt;0.05) and increased p21 expression (p&lt;0.05). Furthermore, stress-induced premature senescence, initiated by serum-deprivation and assessed by SA-β-gal activity and p21 expression, was also amplified in cells cultured on collagenase-resistant collagen. Conclusions: Collagenase-resistant type I collagen induces a premature aging-like syndrome in mice and accelerates both replicative and stress-induced senescence of vascular SMCs. These findings identify a novel, extracellular driver of vascular cell senescence that may underlie plaque instability in aging arteries.
PTGFβ protects p53-null cells from PALA-mediated death
Authors: Mukesh K. Agarwal, Mark W. Jackson, William R. Taylor, Kedar Hastak, Munna L. Agarwal, Stark R. George
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

2958 

The tumor-suppressor p53 is functionally inactivated by mutational, viral, and cellular mechanisms in the majority of human cancers. Therefore, a therapeutic strategy to kill cells lacking functional p53 and simultaneously to protect normal cells would be extremely powerful. Earlier, we reported that an unknown signal, activated in normal cells in response to starvation for pyrimidine nucleotides caused by the aspartate transcarbamylase inhibitor N-phosphonacetyl-L-aspartate (PALA), leads to the rapid activation of p53, which leads in turn to reversible cell cycle arrest. In order to address the mechanism of this phenomenon, wild-type p53 was reintroduced into p53-null ovarian cancer SKOV-3 cells, which undergo apoptosis when treated with PALA. In contrast, PALA-treated p53+/+ (SKP53) cells accumulate in S-phase and are protected. The stable arrest of DNA synthesis by p53 for as long as several weeks is central to protection from PALA-mediated cell death. To identify downstream effectors of this novel S-phase check point mechanism, we developed a comprehensive p53-specific gene chip. Using this and the pair of cell lines SKOV3/SKP53, we found that the activation of p53 by PALA transactivates a gene encoding a secreted protein, PTGFβ also known as prostate differentiation factor or MIC-1. To determine whether PTGFβ is important in protecting PALA-treated cells, we transfected a plasmid carrying a full-length cDNA encoding PTGFβ into p53-null SKOV-3 cells. Individual clones, expressing PTGFβ or not, were treated with PALA. Cells expressing PTGFβ were protected from apoptosis induced by PALA, whereas cells that do not express PTGFβ undergo apoptosis similarly to those lacking p53. We also found that conditioned medium from PTGFβ expressing cells protects SKOV3 cells from PALA-mediated cell death, suggesting that PTGFβ works through an extracellular receptor. In a comparative study, we also observed that treatment withTGFβ2 does not protect SKOV3 cells from PALA-mediated cell death. Therefore, PTGFβ must activate expression of certain protective genes that TGFβ2 does not. These observations establish the role of PTGFβ in p53-mediated protection from DNA damage-induced apoptosis in response to PALA treatment. Our next task is to identify genes selectively induced by PTGFβ whose products are responsible for stable S-phase arrest. Since the utility of PALA as a chemotherapeutic agent in human cancer is limited by toxicity to the gut, it is attractive to consider a strategy in which PALA is combined with PTGFβ in order to improve the therapeutic index.
Abstract 16538: Salt Loading in the Presesnce of Baroreflex Failure Predisposes to Pulmonary Edema in Spontaneously Hypertensive Rat
Authors: Keita Saku, Kazuo Sakamoto, Takamori Kakino, Yasuhiro Oga, Akiko Nishizaki, Masataka Ikeda, Yukimitsu Kuwahara, Takuya Kishi, Kenji Sunagawa
Journal: Circulation (2013)

BACKGROUND:  Patients with heart failure and preserved ejection fraction (HFpEF) are supersensitive to volume overload, and thus pulmonary edema. These patients have a high prevalence of severe arteriosclerosis, baroreflex dysfunction and salt-sensitive hypertension. Baroreflex is by definition regulates arterial pressure (AP), and also is a very powerful regulator of stressed blood volume. We recently demonstrated that deactivating the baroreflex results in striking volume intolerance. In the present study, we examined how baroreflex failure induced by sino-aortic denervation (SAD) and salt loading affect daily fluctuations of left atrial pressure (LAP) in hypertensive model rats.   Methods:  We allocated freely moving 14 weeks old spontaneously hypertensive rats (SHR) (n=16) into 2 groups, SAD or sham operation (Sham). In the following week, we implanted a telemetry system to measure AP and LAP. One week after the second surgery, 2 groups were subjected to either normal (N-salt, 0.5% NaCl) or high salt diet (H-salt, 8% NaCl). We recorded AP and LAP a week after the initiation of N-salt or H-salt diet and generated histograms of LAP distribution for 24 hours.   Results:  SAD did not increase AP (Sham/N-salt:150.6±7.6 vs. SAD/N-salt: 146.4±1.9 mmHg, NS, n=4 for each). However, H-salt increased AP both in Sham and SAD . In LAP histograms, SAD/H-salt increased mean LAP (SAD/H-salt:14.9±2.6 vs. Sham/N-salt: 11.4±1.6 mmHg,  p    CONCLUSIONS:  SAD with high salt intake strikingly increases LAP variations through the volume intolerance and frequently causes high LAP (20% of 24 hours) in SHR. These results strongly suggest that baroreflex failure would play a crucial role in the pathogenesis of pulmonary edema in patients with HFpEF.
AF1q enhances doxorubicin induced apoptosis through mitochondrial apoptotic pathway.
Authors: Ngai Na Co, Wing Pui Tsang, Timothy Wong, Tsun Yee Tsang, Tim Tak Kwok
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2691 

AF1q (ALL1-fused gene chromosome 1q) is an oncogenic factor involved in leukemia development, thyroid tumourigenesis and breast cancer metastasis. The involvement of AF1q in the apoptosis induction has however not yet been demonstrated. In the present study, AF1q is found to be down-regulated in a subline of human squamous carcinoma A431 cells which appeared to be resistant to apoptosis induced by several therapeutic agents. By transient transfection with full-length AF1q cDNA, the sensitivity to doxorubicin, as measured by MTT assay, and the doxorubicin induced apoptosis, by DNA fragementation assay, in A431 cells were found to be increased. In order to elucidate the mechanism for the AF1q regulation of drug induced apoptosis, AF1q stable transfectants were established. By Western blot analysis, the pro-apoptotic Bad was upregulated in the AF1q transfected cells while the expressions of the other apoptotic proteins examined so far were generally not altered. AF1q enhanced the drug induced mitochondrial membrane depolarization as assessed by flow cytometric analysis of cells staining with JC-1. Furthermore, by Western blot analysis, mitochondrial cytochrome c release, activation of caspase-9 and caspase-3 upon doxorubicin treatment were also increased in the AF1q stable transfectants. Collectively, AF1q increases doxorubicin induced apoptosis in A431 cells through activation of mitochondrial apoptotic pathway.
Abstract 1824: Clinical Evaluation of Self Obtained Capillary Blood and Dried Blood Spots for Cyclosporine C0 and C2 Monitoring in Transplant Recipients
Authors: Alexander Leichtle, Georg Martin Fiedler, Gabor Gabel, Uta Ceglarek, Sven Baumann, Helmut Witzigmann, Johann Hauss, Joachim Thiery
Journal: Circulation (2006)

Therapeutic drug monitoring of Cyclosporine (CsA) is an established procedure to maintain the blood drug levels within their respective narrow therapeutic ranges reducing the risk of toxicity and r...
Abstract 13273: Left Ventricular Subepicardial Twist Predicts Left Ventricular Remodeling After Acute Myocardial Infarction
Authors: Elena Abate, Darryl P Leong, Matteo Bertini, Georgette E Hoogslag, M. Louisa Antoni, Victoria Delgado, Eduard R Holman, Hans-Marc J Siebelink, Martin J Schalij, Jeroen J Bax, Nina Ajmone Marsan
Journal: Circulation (2011)

Introduction: Left ventricular (LV) remodeling is a well-known prognostic factor after acute myocardial infarction (AMI). Therefore, early identification of patients prone to develop LV remodeling ...
News and Notes
Authors: D T Thomas
Journal: BMJ (1967)

Outbreaks of this interesting condition, which is associated with bathing in seawater or fresh- water baths infected with the acid-fast bacillus Mycobacterium balnei, have been reported from Sweden, the U.S.A., and Canada'`in the last 15 years, but only two cases have been previously recorded in Britain.'In August of last summer a few persons in Penarth, Glamorganshire, were found to have unusual lesions round the elbow.They were referred to a dermatologist, who came to the conclusion that they were suffering from swimming-pool granuloma.Steps were then taken to alert all general medical practitioners in the area to this condition, and all the schools in the town and neighbourhood were visited and a search made for those suffering from the lesion.This resulted in a large number being referred to the dermatology department of the Cardiff Royal Infirmary.Swimming-pool granuloma was finally confirmed in 73 school- children and 7 adults ; all had bathed at the Penarth indoor salt-water baths.The diag-
Detection of Human Herpesvirus-8 and Epstein-Barr Virus DNA in Primary Intraocular Lymphomas
Authors: Chi-Chao Chan, De Fen Shen, Scott M. Whitcup, Robert B. Nussenblatt, Phuc LeHoang, Francois G. Roberge, Nathalie Cassoux, Carl Herbort, Zhengping Zhuang
Journal: Blood (1999)
Measurement and Prediction of Progress in Delayed Wound Healing
Authors: C J K Bulstrode, A W Goode, P J Scott
Journal: Journal of the Royal Society of Medicine (1987)

Thirty chronic leg ulcers have been studied under controlled conditions until complete healing occurred. Measurement was performed weekly using a computer-linked stereocamera which is capable of measuring skin defects noninvasively with errors of less than 2%. There was a significant difference in healing rate for the first two weeks between clean ulcers entering the trial directly and ulcers admitted first for cleansing before joining the trial. The difference suggests that the weekly healing rate of an ulcer may take up to 2 weeks to respond to a new form of treatment. Absolute ulcer size, change in ulcer size and rate of epithelial migration did not correlate well with time to complete healing, but percentage change in area in the third week was found to be the parameter which gave the earliest close correlation with time to complete healing. Using this parameter, on the data available it was found that time to complete healing could be predicted to within one week for 50% of the ulcers, making this a simple and useful early predictor of treatment efficiency.
Group 2 innate lymphoid cells mediate ozone-induced airway inflammation and hyperresponsiveness in mice
Authors: Qi Yang, Moyar Q. Ge, Blerina Kokalari, Imre G. Redai, Xinxin Wang, David M. Kemeny, Avinash Bhandoola, Angela Haczku
Journal: Journal of Allergy and Clinical Immunology (2015)
Risk Stratification in Brugada Syndrome
Authors: Silvia G. Priori, Maurizio Gasparini, Carlo Napolitano, Paolo Della Bella, Andrea Ghidini Ottonelli, Biagio Sassone, Umberto Giordano, Carlo Pappone, Giosuè Mascioli, Guido Rossetti, Roberto De Nardis, Mario Colombo
Journal: Journal of the American College of Cardiology (2011)
Abstract 12126: Myocardial Extracellular Volume Imaging by MRI Quantitatively Characterizes Myocardial Infarction and Subclinical Myocardial Fibrosis
Authors: Martin Ugander, Abiola J Oki, Li-Yueh Hsu, Peter Kellman, Andreas Greiser, Marcus Y Chen, W P Bandettini, Anthony H Aletras, Andrew E Arai
Journal: Circulation (2010)

Background: Imaging of fibrosis by cardiovascular magnetic resonance (CMR) is routinely performed using late gadolinium enhancement (LGE). However, LGE imaging only visualizes relative differences ...
Bethanidine vs Guanethidine.
Authors: A J Raper, D W Richardson
Journal: Circulation (1978)

To the Editor:We have read with the greatest interest the paper entitled "Ar- teriographic evidence of coronary arterial spasm in acute myocar- dial infarction" by Oliva and Breckinridge (Circulation 56: 366, 1977).This paper clearly demonstrated that, in the first 12 hours of acute myocardial infarction, coronary arterial spasm was super- imposed on a high grade atherosclerotic obstruction in 40% of the cases presented.We have recently performed coronary arteriography on 105 patients 16 days on average after the onset of acute transmural myocardial infarction.1 Our study shows an incidence of 53% of complete occlusion and 47% of stenosis of more than 50%.Our observation of a high number of stenoses in acute transmural myo- cardial infarction supports the hypothesis expressed by Oliva and Breckinridge that the spasm, superimposed on subtotal athero- sclerotic occlusion, can be the initiating factor in the process of acute myocardial infarction.
Abstract 12106: Anomalous Coronary Arteries have More Acute Take-off Angles and Smaller Ostial Areas than Normal Controls: A 64-Detector Coronary Angiography Analysis
Authors: Scott M Pilgrim, Andrew D Blaufox, Saradha Subramanian, Tamara Shashiashvili, Peter Lascarides, Nina Kohn, Amgad N Makaryus
Journal: Circulation (2010)

Background: Coronary artery anomalies (CAA) have been implicated in sudden cardiac death attributed to the presence of acute take-off angles and narrow ostial areas. We hypothesized that left and r...
Computational identification of p53 response elements: Evaluating the (f)utility of comparative genomics approaches
Authors: Monica M. Horvath, Daniel J. Tomso, Michael A. Resnick, Douglas A. Bell
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1550 

The p53 tumor suppressor gene encodes a transcription factor that coordinates cellular responses to DNA damage and stress. Although the human p53 binding site is well-characterized, some genes have consensus-poor p53 response elements (REs) that are nevertheless both necessary and sufficient for transactivation. In such scenarios, comparative genomics is often employed to enhance identification of functional gene regulatory sequence. We evaluated this approach by examining the degree of conservation in 61 experimentally-validated human p53 REs across the canine, murine, and primate lineages. Surprisingly, the average p53 response element is no more conserved than background genomic sequence suggesting that it may evolve to satisfy each species’ unique needs in a changing environment. The common practice of filtering p53 RE predictions by murine conservation would not only increase the false positive rate, but cause numerous bona fide binding sites to be missed. Examination of interspecific sequence diversity as a function of position in the p53 consensus sequence revealed an unexpected excess of diversity in apoptosis-regulating sites, which indicates that they may have been under positive selection for mutation throughout mammalian evolution. Given this, comparative genome analysis between human sequences and their equivalents in a panel of old and new world monkeys may be a promising direction to enhance human p53 binding site prediction accuracy. Overall our analysis cautions against the status quo use of multi-species genome information for prediction of functional regulatory regions. Studies that rely on computational methods to identify functional regulatory regions should ensure that their choice of genomic data is relevant to the selection pressure on those motifs.