tbuckley/cabot-search huggingface dataset:
Abstract 16769: Race to the Top: Are Children With Congenital Heart Disease Off to a False Start?
Authors: Matthew Oster, Alexandra Ehrlich, William T Mahle, Jessica Knight, Bryan Williams
Journal: Circulation (2014)

Background:  Clinical trials and registries have found that children with congenital heart disease (CHD) have poorer neurodevelopment than their unaffected peers. Recent emphasis on mandatory school-based assessment, including as part of the U.S. Department of Education Race to the Top program, provides a unique opportunity to assess how such impairment impacts school performance. The purpose of our study was to evaluate the association of CHD with a) performance on standardized tests and b) the need for special education services.   Methods:  We performed a retrospective cohort study comparing school performance for 438 children born 2002-2003 with a history of surgery for CHD at our institution vs. that of children in our state without CHD. Our two primary outcome measures were a) the % of children meeting standards on the various portions of the 3 rd  grade Criterion Referenced Competency Test and b) the % of children receiving an individualized education plan for special education services in 2008-2011.   Results:  Children with CHD were more likely not to meet standards in math or social studies, but were more likely to meet standards for reading. There were no significant differences in English or science. (Figure) Among those with CHD, presence of a non-cardiac abnormality was a risk factor for not meeting standards (p   Conclusions:  CHD is an important risk factor for poor performance on the math and social studies portions of standardized testing, but increased CHD surgical risk does not translate to poorer school performance. Students with CHD are receiving special education services at increased proportions as compared to their peers, a fact that may explain improved reading performance in those with CHD as compared to their peers.
Abstract 2093: Effect of Metabolic Syndrome on Lipoprotein Subclass Particle Size and Concentration in Postmenopausal Women
Authors: Jerilyn K Allen, Sarah Szanton, Kathleen Lindenstruth, Carol Curtis
Journal: Circulation (2006)

Metabolic syndrome is associated with dyslipidemia and increased cardiovascular risk. The extent to which metabolic syndrome is associated with alterations in lipoprotein subclasses in postmenopaus...
Abstract #5115: Selective Cyclooxygenase Inhibitors Increase Paclitaxel Sensitivity of Taxane-Resistant Ovarian Cancer Cell Lines via Suppression of p-glycoprotein Expression
Authors: Tae Kim, Ji Choi, Jae Lee, Jae Hong, Ho Hahn, Seok Yoon, Yong Kwon, In Lee, Kyung Lim, Ki Lee, Jae Shim, Jung Mok, Haeng Song
Journal: Cancer Research (2009)

Ovarian cancers usually develop chemoresistance after prolonged exposure to chemotherapeutic drugs, such as paclitaxel. Drug resistance is mainly developed via overexpression of p-glycoprotein encoded by multi-drug resistance 1 (MDR1) which effluxes various cytotoxic drugs and inhibit their accumulation within the cell. The expression of MDR1 was shown to be regulated by cyclooxygenase-2 (COX-2), a rate limiting enzyme of prostaglandin (PG) biosynthesis, which plays important roles in tumor development and progression in various human cancers. Thus, we have investigated whether a selective COX-2 inhibitor (NS398) attenuates the expression levels of MDR1 in taxane-resistant human ovarian cancer cell lines (HeyA8-MDR and SKOV3ip2-TR), leading to increased sensitivity to paclitaxel. MTT assay, flow cytometry analyses, Rhodamine 123 efflux assay, Western blotting and realtime RT-PCR were performed. Single treatments of paclitaxel or selective COX inhibitors did not significantly reduce cell viability of HeyA8-MDR and SKOV3ip2-TR. However, combination treatments of paclitaxel with NS398 or even with a selective COX-1 inhibitor (SC560) significantly enhanced paclitaxel sensitivity resulting in increased apoptosis of both cell lines expressing COX-2, but not COX-1. Increased apoptosis in cells treated with paclitaxel and SC560 suggests that COX inhibitor-induced increased sensitivity to paclitaxel in taxane-resistant ovarian cancer cells is PG independent. It is consistent with the result that the addition of PGE 2  did not reverse the synergistic effects of SC560 or NS398 with paclitaxel on cell viability. While selective COX inhibitors did not affect survival of these cell lines, Western blotting and realtime RT-PCR showed that they significantly reduced highly maintained basal levels of MDR1 mRNA and p-glycoprotein, respectively. Furthermore, in combination treatment with paclitaxel, both NS398 and SC560 significantly suppressed paclitaxel-induced overexpression of p-glycoprotein. In conclusion, our results suggest that COX inhibitors could be a potent therapeutic tool to promote paclitaxel sensitization of taxane-resistant ovarian cancer via suppression of p-glycoprotein which mainly contributes efflux of chemotherapeutic agents.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5115.
EGFR-targeted diphtheria toxin kills glioma cells and epithelial cells via distinct apoptotic mechanisms
Authors: A. Corinne Lowe, Tie-Fu Liu, Arthur E. Frankel, Andrew Thorburn
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

4876 

Malignant gliomas, which comprise the majority of the almost 20,000 primary brain cancers that are diagnosed each year in the US, respond very poorly to current therapies with fewer than 20% of patients surviving for more than two years. This dismal prognosis underscores an urgent need to develop improved treatments for this disease. One class of novel therapies that hold promise for treating these cancers are targeted fusion toxins, which consist of a targeting protein such as a growth factor fused to a bacterial toxin such as diphtheria toxin. The fusion toxin is directed to the tumor cells via the targeting molecule, taken into the cells through receptor endocytosis then the toxin is released resulting in tumor cell death. We have previously shown that a recombinant toxin consisting of EGF fused to diphtheria toxin (DAB389EGF) effectively kills glioma cells and this molecule is viewed as a promising agent for treating glioma. However there is little information available regarding the molecular mechanisms through which targeted toxins kill tumor cells. We and others have shown that in other cell types similar toxins kill by inducing caspase-dependent apoptosis. Here we show that DAB389EGF kills both epithelial cells and glioma cells with similar efficiency. However, while epithelial cells display robust caspase activation that is mediated through well known apoptosis regulators, glioma cells treated with DAB39EGF do not activate caspases. The lack of caspase activation was specific to the targeted toxin because other apoptotic stimuli such as Fas ligand could cause robust caspase activation in both glioma and epithelial cells. In agreement with these findings, the morphology of the dying epithelial cells and glioma cells was markedly different as shown by time-lapse microscopy. These data show that targeted diphtheria toxins kill glioma cells through a novel caspase-independent mechanism that is different from their mode of action in other cell types. The mechanism of cell death that is induced by an anti-neoplastic agent can determine the efficacy of a treatment and the type of resistance mechanism that arise. Further studies to determine the mechanism of glioma cell killing should therefore improve our ability to use DAB389EGF and similar targeted toxins to treat gliomas.
Psychiatric diagnosis across cultural boundaries
Authors: Joseph J Westermeyer
Journal: American Journal of Psychiatry (1985)

Diagnosis across cultural boundaries has become a practical rather than an esoteric matter as migration, the number of effective psychiatric therapies, and access to psychiatric care have increased. Cross-cultural diagnosis involves such theoretical considerations as diagnostic categories, pathoplasticity of psychiatric disorder, so-called culture-bound syndromes, "emic" (intracultural) versus "etic" (cross-cultural) conceptual frameworks, and different reporting of symptoms and expression of signs from one cultural group to another. Important clinical issues include distinguishing cultural belief systems from delusions and understanding the special problems of minority, migrant, and refugee patients.
Abstract 6216: Association of “J-Shaped” Curves and Age: A Substudy of the International Verapamil SR-Trandolapril Study (INVEST)
Authors: Scott J Denardo, Franz H Messerli, Juan M Aranda, Rhonda M Cooper-DeHoff, Eileen M Handberg, Yan Gong, Annette Champion, Carl J Pepine
Journal: Circulation (2008)

Our understanding of the expanding population of older patients with coronary artery disease (CAD) and hypertension (HTN) is limited, including information on the relationship between risk for adverse outcomes (death, non-fatal myocardial infarction and non-fatal stroke) and blood pressure (BP). Secondary analysis of data from the International Verapamil-SR-Trandolapril Study (INVEST): Characteristics of clinically stable CAD pts aged ≥50 years with HTN, based upon age in 10-year increments (age  70% with
Fairness is at issue
Authors: R Chadwick
Journal: BMJ (1994)

The last paragraph of Bochner et al's paper asks whether the model and its application are fair. The answer is said to depend on whether rationing itself is fair. And yet arguably the very concept of rationing (as in postwar rationing, for example) involves sharing resources equitably, giving each person their portion. How to achieve an equitable distribution is the issue. In the current debates about allocation of health care resources, however, the term “rationing” has acquired a bad image, whereas “priority setting” has for some reason been thought preferable, although setting priorities precisely does mean giving preference to some areas and thus some people, with the implication that others will go without.

*“Interpersonal comparisons...affect most if not all criteria of allocation.”

The model outlined is one …
miRNA expression profiling in cancer cell lines and tumor samples using LNA™ oligonucleotide arrays
Authors: Erik Wiemer, Mariel Brok, Antonius Boersma, Hans Van Tol, Peter Mouritzen, Mikkel Nørholm, Wilfred Van Ijcken, Kees Nooter
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4170 

MicroRNAs (miRNAs) are a recently recognized class of evolutionarily conserved riboregulators. miRNAs are 21- 22 nucleotides in length and derived from longer precursors. The mature miRNAs function within large complexes to negatively regulate specific target mRNAs. In animals most miRNAs have an imprecise complementarity to their target mRNAs; basepairing with its target sequence - often in the 3’ UTR - results in translational repression. The functional significance of most miRNAs is still unknown as is their involvement in disorders like cancer. The aim of our studies is to determine miRNA expression in cancer cell lines and in series of clinically well-annotated tumor samples and to eventually examine the role of aberrantly expressed miRNAs for the pathogenesis of cancer. Oligonucleotide arrays were developed in which Tm normalized, locked nucleic acid (LNA™) capture probes are used for the detection of the full complement of human/mouse miRNAs as registered and annotated in the miRNA registry ( ). The spotting conditions of the NH2-C6 modified linker with LNA™ capture probes attached, including perfect match and single mismatch oligonucleotides, were determined as were the optimal hybridization and washing conditions. In addition we tested several total RNA and miRNA labeling tech niques including the ULS™-labeling technology (Kreatech Biotechnology) and T4 RNA ligase based methods. We present data on the development, validation and use of these arrays (miRCURY™ arrays) for miRNA expression profiling of cancer cell lines, including chemotherapeutic sensitive and resistant cell lines, as well as samples of breast and lung cancer. Investigated will be whether individual miRNAs or miRNA profiles correlate with important clinical and prognostic parameters such as tumor type, tumor stage, response to chemotherapy, overall and disease free survival. Special attention will be given to the expression of the let-7 family of miRNAs - measured by Northern blotting and quantitative RT-PCR - in non-small cell lung cancer samples and corresponding normal lung tissue in relation to the expression levels of the RAS oncogene.
Abstract 207: Intracoronary Administration of Cardiac Stem Cells Repairs Infarcted Myocardium and Improves Cardiac Function in Rats with Old Infarction
Authors: Xian-liang Tang, Gregg Rokosh, Santosh K SanganalMath, Hiroshi Sato, Buddhadeb Dawn, Qiuli Bi, Shujing Dai, Greg Hunt, Annarosa Leri, Claudia Bearzi, Sumit Tiwari, Gregg Shirk, Piero Anversa, Roberto Bolli
Journal: Circulation (2007)
Abstract 4133: ODM-203, a novel, selective and balanced FGFR and VEGFR inhibitor with strong activity on primary and metastatic tumor growth in FGFR-dependent and angiogenic cancer models
Authors: Tim Holmström, Anu Moilanen, Mari Björkman, Tero Linnanen, Gerd Wohlfahrt, Stefan Karlsson, Riikka Oksala, Timo Korjamo, Susanta Samajdar, Srinivasan Rajagopalan, Shekar Chelur, Kishore Narayan, Raghuveer Ramachandra, Thomas Anthony, Samiulla DS, Murali Ramachandra, Pekka Kallio
Journal: Cancer Research (2015)

Abstract Genomic alterations in fibroblast growth factor receptors (FGFR) and upregulation of vascular endothelial growth factor receptors (VEGFR) are often found in the same cancer types such as gastric, lung and breast and these alterations correlate with patient survival and disease progression. In addition, both FGFR and VEGFR signaling promote tumor angiogenesis. Activation of FGFR signaling has also been described to function as a compensatory angiogenic signal following development of resistance to VEGF inhibition. ODM-203 is a novel and selective inhibitor of the FGFR and VEGFR families exhibiting equal potency to both receptors both in vitro and in vivo. In recombinant kinase assays, ODM-203 inhibits both the FGFR and VEGFR family kinases in the low nanomolar range (IC50 6-35 nM). In cells, ODM-203 suppresses FGFR and VEGFR signaling with similar potency. It also inhibits VEGF-induced endothelial cell (HUVEC) proliferation (IC50 33 nM) with similar potency as it inhibits proliferation in FGFR-dependent cell lines (IC50 50-150 nM). In vivo, ODM-203 shows strong anti-tumor activity in FGFR-dependent xenograft models and in angiogenic xenograft models with similar well tolerated doses. In addition ODM-203 inhibits metastatic tumor growth in angiogenic xenograft models. Lack of activity in a FGFR and VEGFR independent tumor models further supports the selective mode of action of ODM-203. Oral administration of ODM-203 was well tolerated with only FGFR or VEGFR inhibition related physiological events observed in vivo in rat and dog. Based on our findings, ODM-203 has a unique profile with equal potency for both FGFR and VEGFR kinase families which correlates with with strong activity on primary and metastatic tumor growth in FGFR-dependent and angiogenic tumor models. Therefore, a clinical trial with ODM-203 is ongoing in patients with solid tumors (NCT 02264418). Citation Format: Tim Holmström, Anu Moilanen, Mari Björkman, Tero Linnanen, Gerd Wohlfahrt, Stefan Karlsson, Riikka Oksala, Timo Korjamo, Susanta Samajdar, Srinivasan Rajagopalan, Shekar Chelur, Kishore Narayan, Raghuveer Ramachandra, Thomas Anthony, Samiulla DS, Murali Ramachandra, Pekka Kallio. ODM-203, a novel, selective and balanced FGFR and VEGFR inhibitor with strong activity on primary and metastatic tumor growth in FGFR-dependent and angiogenic cancer models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4133. doi:10.1158/1538-7445.AM2015-4133
Abstract 15547: Restoration of Interleukin-10 Levels in Differentiated Mesenchymal Stem Cells Preserves their Immunoprivilege in Allogeneic Implantation and Restores Post-Infarction Cardiac Function
Authors: Sanjiv Dhingra, Jun Wu, Shu-hong Li, Jian Guo, Jim Hu, Richard D Weisel, Ren-Ke Li
Journal: Circulation (2014)

Introduction:  Young healthy donor mesenchymal stem cells (MSCs) are very good candidates for heart repair as they are immunoprivileged and have excellent regenerative capacity. We showed that allogeneic MSCs reduced host immune response and survived early after injection into the ischemic myocardium, but later lost their immunoprivilege and were rejected. Here we show the mechanisms responsible for this immune switch and suggest a way to preserve immunoprivilege and heart function.   Methods/Results:  Allogeneic MSCs were co-cultured with lymphocytes and allo-immune responses were assessed. MSC immunoprivilege was mediated by the immunosuppressive cytokine interleukin-10 (IL-10), as the level of lymphocyte-mediated cytotoxicity was significantly greater for IL-10 knock-out MSCs compared to wild-type. Myogenic differentiation of MSCs led to decreased IL-10 levels and loss of immunoprivilege. Adenovirus-mediated IL-10 gene transfer to differentiated MSCs (DMSCs) decreased cytotoxicity and preserved immunoprivilege. In a rat MI model, allogeneic MSCs transplanted into the infarct region were mostly rejected by 5 weeks. Maintaining IL-10 levels in MSCs prevented anti-donor antibodies against transplanted MSCs and increased cell survival. IL-10 over-expressing MSCs also improved %FS and LV dimensions compared to media injected controls. IL-10 gene therapy in allogeneic MSCs also prevented scar thinning. To investigate further, we co-cultured allogeneic MSCs with lymphocytes for 72h and found that undifferentiated MSCs promoted immune suppression by decreasing lymphocyte proliferation and increasing production of regulatory T cells (Tregs), whereas DMSCs did not inhibit lymphocyte proliferation or induce Treg production. IL-10 over-expression in DMSCs preserved immunoprivilege by decreasing lymphocyte proliferation and by increasing Treg production.   Conclusion:  IL-10 mitigated the recipient’s allo-immune responses against transplanted MSCs. MSC differentiation led to decreased IL-10, reduced ability to suppress cytotoxic lymphocytes, and loss of immune privilege. Maintaining IL-10 levels preserved immune privilege, increased survival of transplanted MSCs and restored cardiac function after MI.
Surveillance of listeriosis in Finland during 1995-2004
Authors: O Lyytikäinen, U M Nakari, S Lukinmaa, E Kela, N Nguyen Tran Minh, A Siitonen
Journal: Eurosurveillance (2006)

We analysed the surveillance data from listeriosis cases notified to the Finnish National Infectious Diseases Register between 1995 and 2004 and describe our recent experience in investigating clusters of listeriosis cases. The number of annual cases varied between 18 and 53 but no trends in incidence were identified (average annual incidence was 7 cases per million inhabitants).
Abstract 10310: Sodium Nitrite is a Pre-Conditioning but Not a Post-Conditioning Agent in a Human Forearm Model of Ischaemia/Reperfusion Injury
Authors: Tom Ingram, Elizabeth Ellins, Julian Halcox, Philip James
Journal: Circulation (2010)

Background: The relatively inert nitric oxide (NO) metabolite nitrite (NO2-) has recently been shown to protect against ischaemia/reperfusion (IR) injury in-vitro. We investigated whether sodium ni...
Abstract 3978: Macrophage Subpopulations are Essential for Infarct Repair With and Without Stem Cell Therapy
Authors: Tamar Ben-Mordechai, Tamar Harel-Adar, Radka Holbova, Natalie Landa-Rouben, Micha S. Feinberg, Zmira Silman, Smadar Cohen, Jonathan Leor
Journal: Circulation (2009)
Abstract 19913: In vivo Characterization of a New Abdominal Aortic Aneurysm (AAA) Mouse Model with Conventional and Molecular MRI
Authors: Ahmed Klink, Joeri Heynens, Beatriz Herranz, Erik Sanders, Gustav Strijkers, Maarten Merkx, Klaas Nicolay, Valentin Fuster, Ziad Mallat, Willem J Mulder, Zahi A Fayad
Journal: Circulation (2010)

The turnover of collagen plays a critical role in the pathogenesis, progression and rupture of Abdominal Aortic Aneurysms (AAA). Non-invasive imaging of this process may represent an opportunity to...
Abstract 1372: Characterization Of The Rejuvenation Of Cardiac Sympathetic Nerves In Cardiac Hypertrophy
Authors: Kensuke Kimura, Masaki Ieda, Hideaki Kanazawa, Takahide Arai, Takashi Kawakami, Takeshi Onizuka, Toshimi Kageyama, Yohei Ohno, Sung Han Yoon, Shinji Makino, Motoaki Sano, Satoshi Ogawa, Keiichi Fukuda
Journal: Circulation (2007)

Background : Cardiac hypertrophy induces the fetal isoform of genes (rejuvenation), including contractile proteins, ion channels, and natriuretic peptides. Cardiac sympathetic nerve function is known to be altered in cardiac hypertrophy and congestive heart failure. We recently reported that alteration of cardiac sympathetic nerves (CSN) was caused by their rejuvenation (Circ Res, 2007). The present study was designed to examine the precise characterization of the rejuvenation of CSN in cardiac hypertrophy. Methods and Results : RV hypertrophy was produced by consistent hypoxia (10% O 2 ) in C57/BL6 mice. RV pressure increased to 47 mmHg, and RV/(body weight) ratio increased by 1.6 fold. Nerve growth factor protein was augmented in hypertrophic RV, but was unchanged in LV. Double-transgenic mice, which specifically express eGFP (enhanced green fluorescent protein) in the sympathetic neurons, was generated by crossing dopamine β-hydroxylase (DBH)-Cre mice with Floxed-eGFP mice. The eGFP-positive CSN were markedly increased in hypertrophic RV, but not in LV. Nerve density, quantitated by immunostained area with eGFP and GAP43 (growth-associated corn marker), increased by 8.1 and 9.3 fold, respectively, in RV, but not in LV. (4) Catecholamine content was attenuated in RV. (5) Western blot revealed that tyrosine hydroxylase was markedly down-regulated in RV. (6) Immunostaining clearly demonstrated that the immature neuron markers, PSA-NCAM (highly polysialylated neural cell adhesion molecule) and Ulip-1 (Unc-33-like phosphoprotein 1), were expressed in CSN in hypertrophic RV and stellate ganglia. Basic helix-loop-helix transcription factor, Mash-1 (mammalian achaete-scute complex homolog 1) was strongly expressed in the stellate ganglia. (7) Immature neuron marker-immunopositive cells in stellate ganglia had a markedly decreased TH expression. Conclusion : The rejuvenated CSN showed various immature and fetal neuron marker genes at not only the peripheral axons but also the cellular bodies at the stellate ganglia. Rejuvenation of CSN might be critically involved in the alteration of sympathetic neuronal function in cardiac hypertrophy, including depressed norepinephrine synthesis and hyperinnervation.
Handling scientific fraud
Authors: R P Husemeyer
Journal: BMJ (1995)

Pearce's editors were not to blame

EDITOR,--In his editorial on the Pearce affair Stephen Lock states that the review of the clinical trial was clearly inadequate.1 He is amazed at the credulity that the British Journal of Obstetrics and Gynaecology showed in publishing the trial, on the basis of his observation that over three years Pearce purported to have collected 191 women with a syndrome so uncommon that a major referral centre (unnamed) saw only one or two new …