tbuckley/cabot-search huggingface dataset:
Participation of Central Noradrenergic Neurons in Arterial Baroreceptor Reflexes in the Rabbit: A STUDY WITH INTRACISTERNALLY ADMINISTERED 6-HYDROXYDOPAMINE
Authors: J. P. CHALMERS, J. L. Reid
Journal: Circulation Research (1972)

Rabbits were given intracisternal injections of 6-hydroxydopamine (6-OH-DA) that caused selective ablation of central noradrenergic neurons without damaging peripheral sympathetic nerves. Administration of 6-OH-DA (600 µg/kg, intracisternally) to normal rabbits produced a permanent bradycardia of about 30%, which was initiated centrally and mediated mainly through the vagus, and caused a brief reduction in mean arterial blood pressure, which was due to transient withdrawal of alpha-sympathetic tone. Treatment with 6-OH-DA (600 µg/kg) completely prevented the increases in arterial blood pressure seen on the seventh and the fourteenth day after sinoaortic denervation in control rabbits, although there was a transient increase in blood pressure for 1 day after denervation in the group treated with 6-OH-DA. Central norepinephrine concentrations were reduced in all areas, especially in the spinal cord (to less than 10% of control), in the denervated rabbits treated with 6-OH-DA compared with the levels in denervated controls. When 6-OH-DA (600 µg/kg, intracisternally) was given to rabbits with neurogenic hypertension produced by buffer nerve section, it caused an immediate and persistent return of pressure to the level that existed before denervation. Probably, the integrity of central noradrenergic neurons is necessary for the development of sustained increases in arterial blood pressure following sinoaortic denervation. We suggest that central noradrenergic nerves form an essential link in the baroreceptor reflex arc, possibly at the bulbospinal level.
Abstract 2623: The role of polymorphisms in DNA repair genes and HPV 16 integration status in cervical dysplasia
Authors: E. Susan Amirian, Deborah Marquez-Do, Karen Adler-Storthz, Michele Follen, Michael E. Scheurer
Journal: Cancer Research (2012)

Abstract BACKGROUND: Cervical cancer is the second leading cause of death in women worldwide, and yet, little is understood about why some HPV-infected women develop cancerous lesions while others are able to clear the infection with no sequelae. Previous evidence has indicated that HPV integration status may be associated with cervical cancer development and progression. However, host genetic variation within genes that may play important roles in the viral integration process has been understudied. The purpose of this study was to examine the association between both HPV 16 viral integration status and single nucleotide polymorphisms (SNPs) in non-homologous end-joining (NHEJ) DNA repair pathway genes on cervical dysplasia, comparing women with no dysplasia to those with low-grade or high-grade squamous intraepithelial lesions. METHODS: A total of 765 women were selected from two large trials designed to evaluate optical technologies for cervical cancer, being conducted at MD Anderson Cancer Center, Lyndon B Johnson General Hospital, and the British Columbia Cancer Agency. Genotyping was conducted using the Illumina Golden Gate platform; individuals with call rates &amp;lt;85% were excluded from the analyses. HPV integration status was determined using an assay described in the literature. Chi-square and Fisher's exact tests were conducted to determine which SNPs were significantly associated with normal cytology, low-grade, or high-grade lesions. Among participants with cervical dysplasia, chi-square tests and polytomous logistic regression models were used to evaluate the effect of each polymorphism on viral integration status. We used an additive genetic model for all tests. P-values were adjusted using the false discovery rate method and FDR-adjusted q values are reported. RESULTS: Women with high-grade lesions were significantly younger than women with low-grade or no lesions. Tag-SNPs in 13 DNA repair genes, including RAD50, WRN, and XRCC5, were significantly associated with cervical dysplasia. HPV16 integration status was differential across cervical cytology, but overall, most participants had a mix of both episomal and integrated HPV 16. Four tag-SNPs in the XRCC4 gene were found to be significantly associated with HPV 16 integration status. CONCLUSION: Our findings indicate that host genetic variation in NHEJ DNA repair pathway genes, specifically XRCC4, are significantly associated with HPV integration, and that these genes may play an important role in determining cervical cancer development and progression. This is the first time that host genetic variation has been linked to the viral integration event. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2623. doi:1538-7445.AM2012-2623
Abstract 3337: IL-6 and IL-8 stimulation of breast cancer stem cells contributes to trastuzumab resistance following PTEN deletion
Authors: Korkaya Hasan, April Davis, Gwangil Kim, Ahmet A. Quraishi, Amanda K. Paulson, Susan Chung, Rosemarie C. D'Angelo, Suling Liu, Tahra Luther, Shawn G. Clouthier, Max S. Wicha
Journal: Cancer Research (2011)

Abstract Recent studies strongly implicated breast cancer stem cells (CSC) in therapeutic resistance and recurrence. Despite the benefits of HER2 targeted therapeutics including trastuzumab for the treatment of HER2 amplified breast cancer, one third of tumors do not respond and resistance develops in patient with chronic exposure. Although the mechanisms mediating HER2 resistance have not been completely elucidated, there is evidence that PTEN deletion plays a role. We have previously demonstrated that HER2 regulates the breast cancer stem cell population through regulation of Akt signaling resulting in Wnt activation. In order to investigate the mechanisms of trastuzumab resistance, we overexpressed HER2 and/or knocked down PTEN in luminal MCF7 and basal SUM159 breast cancer cells. In addition, we knocked down PTEN in two HER2 amplified breast cancer cell lines BT474 and SKBR3. In each case, PTEN knock down increased the CSC population as determined by the Aldefluor assay as well as markedly increasing the production of the cytokines IL-6 and IL-8. Cytokine production was partially mediated through Akt activation of NF-κB. Short term trastuzumab treatment decreased the CSC population in HER2 amplified breast cancer cell lines, an effect that was completely abrogated by PTEN knockdown. Long term trastuzumab treatment of HER2 amplified and PTEN deleted cell lines generated resistant populations that secreted significantly elevated levels of IL-6 and IL-8. In vivo, intrinsically or experimentally amplified HER2 cells with PTEN knockdown were highly tumorigenic and produced metastasis in multiple organs. We previously demonstrated that the Akt inhibitor perifosine is able to reduce CSCs in PTEN-deleted tumors. In order to examine the role of IL-6 and IL-8 in mediating trastuzumab resistance, we treated mice bearing HER2 overexpressing PTEN deleted xenografts with perifosine alone or in combination with an anti-IL-6 receptor and/or anti-IL-8 antibodies. Tumor growth was substantially suppressed by the addition of IL-6 and IL-8 targeting antibodies. These studies suggest that resistance to trastuzumab in PTEN deleted cells may be partially mediated by the activation of cytokine loops involving IL-6 and IL-8. The use of agents which block these cytokine loops may provide a novel approach to overcome trastuzumab resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3337. doi:10.1158/1538-7445.AM2011-3337
P595PDGFRalpha demarcates the cardiogenic and clonogenic Sca-1+ stem cell
Authors: M Noseda, M Harada, S Mcsweeney, T Leja, E Belian, I Macaulay, M Abreu Paiva, SE Jacobsen, M Barahona, MD Schneider
Journal: Cardiovascular Research (2014)

Cardiac progenitor/stem cells in adult hearts are a potential mode of self-repair, therapeutic product, and target for activation in situ, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT-PCR and clonal analyses, we define four sub-populations in adult mouse myocardium sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, platelet/endothelial cell adhesion molecule 1 (CD31), and platelet derived growth factor receptor-α (PDGFRα). SP status predicted clonogenicity plus cardiogenic genes' expression (Gata4/6, Hand2, Tbx5/20), properties segregating more specifically to PDGFRα+ cells. PDGFRα- cells were characterized, instead, by Kdr/Flk1, Cdh5, CD31 and lack of clone formation. Clonal progeny of single Sca1+ SP cells showed tri-lineage potential (cardiomyocyte, endothelial, smooth muscle) after cardiac grafting. By fate-mapping, PDGFRα+ CD31- cells derived from cells formerly expressing Mesp1, Nkx2-5, Isl1, Gata5 and Wt1, distinct from PDGFRα- CD31+ cells (Gata5, Wt1 low; Flk1, Tie2 high). Thus, PDGFRα demarcates the clonogenic cardiogenic Sca-1+ stem cell.
NT-10 * IDENTIFICATION OF AURINTRICARBOXYLIC ACID (ATA) AS AN INHIBITOR OF TWEAK-Fn14 SIGNALING IN GLIOBLASTOMA CELLS
Authors: H. Dhruv, I. Mathews, D. Chow, H. Yin, M. Berens, N. Tran
Journal: Neuro-Oncology (2014)

The long-term survival of patients with glioblastoma (GB) is compromised by the proclivity for local invasion into the surrounding normal brain, escaping surgical resection and contributing to therapeutic resistance. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor superfamily, can stimulate glioma cell invasion via binding to fibroblast growth factor-inducible 14 (Fn14) and subsequent activation of the transcription factor NF-κB. In order to discover a small molecule inhibitors that disrupt Fn14-TWEAK signaling axis and subsequently glioma cell invasion, we developed a cell-based drug screening assay using HEK293 cells that overexpresses Fn14 and harbors NF-κB driven Firefly luciferase protein expression. In preliminary drug screening assay using LOPAC1280 library of 1280 pharmacologically active compound, Aurintricarboxylic Acid (ATA) showed suppression of NF-κB driven Firefly Luciferase activity downstreatm of TWEAK-Fn14 signaling. Conversely, ATA did not show any suppression in NF-κB driven Firefly Luciferase activity downstream of TNFα-TNFR1 signaling, suggesting that ATA is a specific inhibitor of TWEAK-Fn14-NFκB signaling. In vitro, we demonstrated that ATA suppresses TWEAK induced chemotactic migration of glioma cells (T98G and A172) by inhibiting Rac1 and Akt activation. In addition, glioma cells treated with ATA showed increased susceptibility to standard treatment including temozolomide and radiation. In summary, this work reports a new small molecule inhibitor of TWEAK-Fn14 signaling that could be useful in enhancing the therapeutic targeting of this deadly disease.
DIFFERENTIAL CHANGES IN PLAQUE BEHIND THE STENT AFTER BARE-METAL AND DRUG-ELUTING STENT IMPLANTATION IN HUMANS: IMPLICATIONS FOR LATE STENT FAILURE?
Authors: Ioannis Andreou, Koki Shishido, Antonios Antoniadis, Saeko Takahashi, Masaya Tsuda, Michail Papafaklis, Shingo Mizuno, Ahmet Coskun, Shigeru Saito, Elazer Edelman, Charles Feldman, Peter Stone
Journal: Journal of the American College of Cardiology (2015)
Abstract 4638: Over-expression of p19 protein in human gastric carcinoma and its clinicopathological significance
Authors: Ming-Ming Tsai, Chia-Siu Wang, Kwang-Huei Lin
Journal: Cancer Research (2010)

Abstract Gastric cancer is the fifth leading cause of cancer-related death in Taiwan. Identification of gastric cancer related factor is essential to increase patient survival. P19 protein was identified using two-dimensional electrophoresis (2-DE) combined with Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometer (MALDI-TOF MS) and isobaric tag for relative and absolute quantitation (iTRAQ). We evaluated the p19 protein expression as a potential biomarker of gastric cancer since it aberrantly expressed in gastric cancer and associated with metastasis. Tumor tissue and matching noncancerous mucosa were obtained from 60 patients immediately after gastric resection. P19 protein expression levels were determined by quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR) and Western blot. The expression of p19 was up-regulated 76.3% of 55 patients, or 45% of 60 patients with gastric cancer in tumor tissues (compared with adjacent non-tumor tissues) at mRNA or protein levels, respectively. Paraffin-fixed tumor tissues were used for immunohistochemistry (IHC) study in 110 patients with gastric cancer. The p19 protein was up-regulated in about 58% tumor tissues, however, not in plasma. The clinic-pathological correlation of p19 protein was also valuated. The higher p19 expressions were significantly associated with lymph node metastasis, and were significantly higher in the stages of III and IV than those in the stages I and II. The depth of wall invasion was significantly greater in the stage of (T3 and T4) compared to the (T1 and T2). Five-year survival of patients with lower p19 expression was significantly better than those patients with a higher expression. To better understand the function of p19 protein in human gastric cancer cells, the isogenic p19 protein overexpressing cell lines (AZ521, SC-M1) were prepared. The proliferative, migratory and invasive abilities were increased in the p19 overexpressing cell lines. The results indicate the p19 protein is a potential prognostic marker for gastric cancer and its function associates with cell invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4638.
Abstract 3452: The role of CX3CR1 in resistance of ovarian carcinoma cells to radiation therapy
Authors: Jia Xie, Maria Barbolina
Journal: Cancer Research (2012)

Abstract Ovarian carcinoma is a leading cause of death from gynecologic malignancies. The current standard of care, a combination of chemotherapy and radiation, fails to keep patients in remission. Thus, modifications of the therapy and the combinations with the new molecular biological technologies are crucial for the development of the modernized approaches to combat this disease. Previous attempts to use radiotherapy as an additional treatment was not successful mainly due to the dose-related side effects, as well as radioresistance. Therefore, mechanistical understanding of the biology of ovarian carcinoma could offer ways to overcome current problems. Fractalkine receptor (CX3CR1) belongs to a chemokine family of G protein-coupled receptors, the most frequently and successfully drug-targeted group of proteins. Interaction of chemokines with their receptors plays a pivotal role in homing distant metastasis, as well as promoting migration, adhesion, and proliferation in many types of cancer. This project is aimed at understanding the role of CX3CR1 in sensitization of epithelial ovarian cancer cells to radiotherapy. Our data indicate that downregulation of CX3CR1 in ovarian carcinoma cells leads to approximately 50% sensitization to x-ray radiation, as determined by the clonogenic ability assay. Our Western blotting and immunofluorescence analysis data also show that downregulation of CX3CR1 results in accumulation of DNA damage at lower doses. Thus, our data indicate that disruption of the CX3CR1 signaling could sensitize ovarian carcinoma to radiation therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3452. doi:1538-7445.AM2012-3452
ATM Gene Discovery May Quiet Carrier Cancer Risk Debate
Authors: J. Randal
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article ATM Gene Discovery May Quiet Carrier Cancer Risk Debate Get access Judith Randal Judith Randal Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 18, 20 September 1995, Pages 1350–1351, https://doi.org/10.1093/jnci/87.18.1350 Published: 20 September 1995
ERGOREFLEX OVERACTIVITY: A POTENTIAL CAUSE OF EXERCISE LIMITATION AND DYSAUTONOMIA IN PATIENTS WITH MITOCHONDRIAL MYOPATHY
Authors: Alberto Aimo, Alberto Giannoni, Massimo Piepoli, Michelangelo Mancuso, Gabriele Siciliano, Claudio Passino, Michele Emdin
Journal: Journal of the American College of Cardiology (2016)
A2.19 IL-17A-low CCR6+ TH cell populations of patients with rheumatoid arthritis are pathogenic, multidrug resistant and associated with dmard and glucocorticoid treatment response
Authors: JP van Hamburg, SMJ Paulissen, N Davelaar, JMW Hazes, E Lubberts
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> CCR6<sup>+</sup> T-helper (Th) cells and their pro-inflammatory cytokines, including IL-17A, are implicated in the pathogenesis of rheumatoid arthritis (RA). However, within CCR6<sup>+</sup> Th cells various subpopulations are present and their clinical relevance in RA is unclear. Therefore, we characterised CCR6<sup>+</sup> Th subpopulations with regard to pathogenic potential and disease-modifying antirheumatic drugs (DMARDs) and glucocorticoid (GC) therapy outcome in RA. <h3>Material and methods</h3> Within total CCR6<sup>+</sup> Th cells from patients with RA, CCR4<sup>+</sup>CXCR3<sup>-</sup> (Th17), CCR4<sup>-</sup>CXCR3<sup>+</sup> (Th17.1), CCR4/CXCR3 double-positive (DP) and double-negative (DN) cells were distinguished and/or sorted by flow cytometry. These subpopulations were: analysed for Th17/Th1-associated factors; co-cultured with RA-derived synovial fibroblasts (RASF); related to disease-modifying antirheumatic drugs (DMARDs) and glucocorticoid (GC) therapy response; analysed regarding the expression of multidrug transporters MDR1 and MRP1 and drug efflux potential. <h3>Results</h3> All these populations expressed the transcription factor RORC and were present in RA peripheral blood and synovial fluid. Despite differential IL-17A, IL-17F, IFNg and TBX21 expression, all subpopulations, including the IL-17A low-producing Th17.1, DP and DN cells, showed pathogenic activity in the induction of IL-1β, IL-6, IL-8, COX-2 and MMP-3 expression by synovial fibroblasts. MDR1 (ABCB1) and MRP1 (ABCC1) are cellular efflux transporters of glucocorticoids and the DMARD methotrexate. In particular Th17.1 and DN cells expressed relatively high levels of MDR1, whereas MRP1 was expressed at similar levels among the subpopulations. Interestingly, increased drug efflux potential by CCR6<sup>+</sup> Th cells, as measured by rhodamine123 and calcein transport, was associated with the lack of DMARD/GC therapy response. <h3>Conclusions</h3> Therefore, we conclude that in addition to IL-17-<sup>high</sup> Th17 cells, IL-17-<sup>low</sup> CCR6<sup>+</sup> Th cells display pathogenic activity in the context of RA. Moreover, we identified efflux transporter expression and efflux activity by RA CCR6<sup>+</sup> Th cells. These findings suggest that pathogenic and multidrug resistant CCR6<sup>+</sup> Th cells are associated with the lack of DMARD/GC therapy response in patients with RA.
P125 Digital Measurement Strategy is Robust in Non-Expert Hands in Measuring Clinically Relevant Effusions on Chest Radiograph
Authors: M Nagendran, RJ Hallifax, M Maruthappu, A Manuel, NM Rahman
Journal: Thorax (2012)

<h3>Introduction</h3> The primary outcome of most studies investigating pleural infection treatment is the pleural effusion volume change between two defined time points. This may be performed using thoracic computed tomography (CT) scans, but this method is costly and involves increased radiation to the patient. Data from the MIST-2 trial demonstrates that a digital chest radiograph measurement strategy was effective and correlated well with CT scanning. <h3>Aim</h3> To assess deviation of novice scorers from an expert scorer when measuring pleural effusion size on chest radiographs using the digital scoring system. <h3>Methods</h3> 132 chest radiograph digital images (JPEG format) were obtained from the 3 month follow-up of the MIST-2 trial. The optimal method was observer-estimated position of diaphragm and mediastinum with mediastinum discounted from the measurement. For each image, the area occupied by the pleural collection and hemithorax was manually drawn as a polyhedron, permitting calculation of percentage area occupied by effusion. Medical students acted as novice scorers and a respiratory specialist was the expert scorer and both independently scored the images. <h3>Results</h3> Clinically significant effusions were defined as those over 2% of the hemithorax area. 73 of 132 were rated by the expert as not clinically significant. Of the remaining 59, there was &gt;2% difference between novice and expert scores in 38 cases. Novice and expert then reassessed these radiographs together to agree a consensus. Within the subgroup of 59 clinically significant effusions, the mean difference between the novice and expert scores was –0.10 (95% CI –3.2 to 3.0, p=0.95). Comparison of novice and expert respectively to the final consensus scores revealed a significant mean difference in the novice scores of 2.0 (95% CI 0.02 to 4.0, p=0.048, expert: –0.11, 95% CI –1.85 to 1.63, p=0.90). <h3>Conclusions</h3> Novice scorers have a tendency to overestimate effusion size. However, where there is a clinically significant (&gt;2% of hemithorax) effusion, scores between novice and expert correlate well. This implies that the digital measurement strategy is robust in non-expert hands in measuring clinically relevant effusions. This digital chest radiograph assessment tool is therefore a potential simple outcome for use in future studies assessing pleural drainage.
Major Cancer Screening Trial Launched in 10 U.S. Centers
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Major Cancer Screening Trial Launched in 10 U.S. Centers Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 23, 1 December 1993, Page 1903, https://doi.org/10.1093/jnci/85.23.1903 Published: 01 December 1993
When to simulate and when to associate? Accounting for inter-talker variability in the speech signal
Authors: Alison M Trude
Journal: Behavioral and Brain Sciences (2013)

Pickering & Garrod's (P&G's) theory could be modified to describe how listeners rapidly incorporate context to generate predictions about speech despite inter-talker variability. However, in order to do so, the content of "impoverished" predicted percepts must be expanded to include phonetic information. Further, the way listeners identify and represent inter-talker differences and subsequently determine which prediction method to use would require further specification.