tbuckley/cabot-search huggingface dataset:
Complex Formation and Function of Estrogen Receptor α in Transcription Requires RIP140
Authors: Meritxell Rosell, Ekaterina Nevedomskaya, Suzan Stelloo, Jaya Nautiyal, Ariel Poliandri, Jennifer H. Steel, Lodewyk F.A. Wessels, Jason S. Carroll, Malcolm G. Parker, Wilbert Zwart
Journal: Cancer Research (2014)

Abstract RIP140 is a transcriptional coregulator involved in energy homeostasis, ovulation, and mammary gland development. Although conclusive evidence is lacking, reports have implicated a role for RIP140 in breast cancer. Here, we explored the mechanistic role of RIP140 in breast cancer and its involvement in estrogen receptor α (ERα) transcriptional regulation of gene expression. Using ChIP-seq analysis, we demonstrate that RIP140 shares more than 80% of its binding sites with ERα, colocalizing with its interaction partners FOXA1, GATA3, p300, CBP, and p160 family members at H3K4me1-demarcated enhancer regions. RIP140 is required for ERα-complex formation, ERα-mediated gene expression, and ERα-dependent breast cancer cell proliferation. Genes affected following RIP140 silencing could be used to stratify tamoxifen-treated breast cancer cohorts, based on clinical outcome. Importantly, this gene signature was only effective in endocrine-treated conditions. Cumulatively, our data suggest that RIP140 plays an important role in ERα-mediated transcriptional regulation in breast cancer and response to tamoxifen treatment. Cancer Res; 74(19); 5469–79. ©2014 AACR.
Excessive Fibrin Deposition in Nasal Polyps Caused by Fibrinolytic Impairment through Reduction of Tissue Plasminogen Activator Expression
Authors: Tetsuji Takabayashi, Atsushi Kato, Anju T. Peters, Kathryn E. Hulse, Lydia A. Suh, Roderick Carter, James Norton, Leslie C. Grammer, Seong H. Cho, Bruce K. Tan, Rakesh K. Chandra, David B. Conley, Robert C. Kern, Shigeharu Fujieda, Robert P. Schleimer
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Nasal polyps (NPs) are characterized by intense edema or formation of pseudocysts filled with plasma proteins, mainly albumin. However, the mechanisms underlying NP retention of plasma proteins in their submucosa remain unclear.We hypothesized that formation of a fibrin mesh retains plasma proteins in NPs. We assessed the fibrin deposition and expression of the components of the fibrinolytic system in patients with chronic rhinosinusitis (CRS).We assessed fibrin deposition in nasal tissue from patients with CRS and control subjects by means of immunofluorescence. Fibrinolytic components, d-dimer, and plasminogen activators were measured using ELISA, real-time PCR, and immunohistochemistry. We also performed gene expression and protein quantification analysis in cultured airway epithelial cells.Immunofluorescence data showed profound fibrin deposition in NP compared with uncinate tissue (UT) from patients with CRS and control subjects. Levels of the cross-linked fibrin cleavage product protein, d-dimer, were significantly decreased in NP compared with UT from patients with CRS and control subjects, suggesting reduced fibrinolysis (P < 0.05). Expression levels of tissue plasminogen activator (t-PA) mRNA and protein were significantly decreased in NP compared with UT from patients with CRS and control subjects (P < 0.01). Immunohistochemistry demonstrated clear reduction of t-PA in NP, primarily in the epithelium and glands. Th2 cytokine-stimulated cultured airway epithelial cells showed down-regulation of t-PA, suggesting a potential Th2 mechanism in NP.A Th2-mediated reduction of t-PA might lead to excessive fibrin deposition in the submucosa of NP, which might contribute to the tissue remodeling and pathogenesis of CRS with nasal polyps.
Assessing HER2 gene amplification as a potential target for therapy in invasive urothelial bladder cancer with a standardized methodology: results in 1005 patients
Authors: M. Laé, J. Couturier, S. Oudard, F. Radvanyi, P. Beuzeboc, A. Vieillefond
Journal: Annals of Oncology (2009)

This study assessed the human epidermal growth factor receptor-2 (HER2) protein expression and its relationship with gene amplification in invasive bladder carcinoma, using the same criteria than for breast cancer.In 1005 patients, paraffin-embedded tissues of transurethral resection or cystectomy were evaluated by immunohistochemistry (IHC), using antibodies against HER2. All samples with a 2+ or 3+ HER2 overexpression were evaluated by FISH.HER2 overexpression was observed in 93 (9.2%) tumors (2+: 42 tumors and 3+: 51 tumors). Using FISH, all HER2 3+ tumors had a gene amplification, whereas no amplification was found in 2+ tumors. Intratumoral heterogeneity was observed in 35% of cases. These tumors showed the same heterogeneous pattern, with adjacent 3+ positive and negative areas by both IHC and FISH.This study showed that 5.1% of invasive bladder carcinomas had a HER2 gene amplification. These findings may have clinical implications for the management of patients with HER2-positive locally advanced or metastatic bladder cancer, as they could be potential candidates for targeted therapy.
Assessing neurotoxicity from the low-dose radiation component of radiosurgery using magnetic resonance spectroscopy
Authors: C. R. Kelsey, S. Mukundan, Z. Wang, C. A. Hahn, B. J. Soher, J. P. Kirkpatrick
Journal: Neuro-Oncology (2010)

The aim of the study was to determine if biochemical changes indicative of injury, assessed using magnetic resonance spectroscopic imaging (SI), are observed after stereotactic radiosurgery (SRS). The study included patients who underwent SI immediately before and 1, 30, and 90 days following SRS. Short TE spectra (TR/TE 1000/35 ms) were acquired at the SRS isocenter with a 2D PRESS-CSI sequence on a single 1.5 T scanner. The SRS isodose lines were overlaid on the magnetic resonance imaging slice utilized for SI data acquisition. N-Acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were computed for multiple voxels located between the 25 and 50 cGy isodose lines (low dose) and the 200 and 350 cGy isodose lines (medium dose). An analysis of variance and paired t-tests compared metabolite levels at different time points. Twelve patients were enrolled, although 3 were excluded secondary to poor spectral data quality or deviations from the prescribed SI protocol. The median number of voxels analyzed from the low- and medium-dose region was 7 and 4, respectively. No significant changes in metabolite peak height ratios over time were seen in the low-dose region, for either NAA/Cr (P = .89) or Cho/Cr (P = .85). There was no difference in Cho/Cr peak height ratios in the medium-dose region (P = .62). There was an increase in the NAA/Cr peak height ratio in the medium-dose region between day −1 and day +30 (P = .003), followed by a decline to baseline between days +30 and +90 (P = .03). We did not observe a significant decline in NAA/Cr or change in Cho/Cr peak heights in uninvolved brain parenchyma after SRS.
Gene Conversion as a Source of Nucleotide Diversity in Plasmodium falciparum
Authors: K. M. Nielsen
Journal: Molecular Biology and Evolution (2003)

Examination of polymorphisms in the Plasmodium falciparum gene for falcipain 2 revealed that this gene is one of two paralogs separated by 10.8 kb in chromosome 11. We designate the annotated gene denoted chr11.gen_424 as encoding falcipain 2A and the annotated gene denoted chr11.gen_427 as encoding falcipain 2B. The paralogs are 96% identical at the nucleotide level and 93% identical at the amino acid level. The consensus sequences differ in 31/309 synonymous sites and 45/1140 nonsynonymous sites, including three amino acid replacements (V393I, A400P, and Q414E) that are near the catalytic site and that may affect substrate affinity or specificity. In six reference isolates, among 36 synonymous sites and 46 nonsynonymous sites that are polymorphic in the gene for falcipain 2A, falcipain 2B, or both, significant spatial clustering is observed. All but one of the polymorphisms appear to result from gene conversion between the paralogs. The estimated rate of gene conversion between the paralogs may be as many as 1,400 to 1,700 times greater than the rate of mutation. Owing to gene conversion, one of the falcipain 2A alleles is more similar to the falcipain 2B alleles than it is to other falcipain 2A alleles. Divergence among the synonymous sites suggests that the paralogous genes last shared a common ancestor 15.2 MYA, with a range of 8.8 to 20.6 MYA. During this period, the paralogs have acquired 0.10 synonymous substitutions per synonymous site in the coding region. The 5′ and 3′ flanking regions differ in 47.7% and 39.8% of the nucleotide sites, respectively. Hence synonymous sites and flanking regions are not conserved in sequence in spite of their high AT content and T skew.
A randomized double-blind trial to compare the clinical efficacyof granisetron with metoclopramide, both combined with dexamethasone in the prophylaxis of chemotherapy-induced delayed emesis
Authors: M.S. Aapro, B. Thuerlimann, C. Sessa, C. de Pree, J. Bernhard, R. Maibach
Journal: Annals of Oncology (2003)
Mucosal biotransformation rates in the small intestine of children.
Authors: M R Stahlberg, E Hietanen, M Maki
Journal: Gut (1988)

Biotransformation of ingested xenobiotics is known to take place in the gastrointestinal mucosa of laboratory animals and adult humans as well as in the liver. We studied the activities of aryl hydrocarbon hydroxylase, epoxide hydrolase, and glutathione peroxidase in 242 peroral small intestinal biopsy samples of children aged eight months to 18 years: 201 with normal histology, 21 with partial villous atrophy, and 20 with severe villous atrophy. All these enzymes were detectable even in the youngest children. The aryl hydrocarbon hydroxylase activity was age dependent, while the other measured enzyme activities were not related to the age of the patients. The aryl hydrocarbon hydroxylase activity was not related to the mucosal histology, but the epoxide hydrolase and glutathione peroxidase activities were diminished in samples with severe villous atrophy as compared with normal mucosa. This suggests that small intestinal mucosa with villous atrophy may produce oxidated, reactive metabolites, but further metabolism into detoxication products is decreased. This may expose persons with mucosal atrophy to possible harmful effects of environmental xenobiotics entering the body even at low doses.
Chronic liver disease in the Alexandria governorate, Egypt: contribution of schistosomiasis and hepatitis virus infections
Authors: Mario Angelico, Elil Renganathan, Claudia Gandin, Moustafa Fathy, M. Cristina Profili, Wael Rafai, Adriano De Santis, Ali Nagi, Gamal Amin, Livio Capocaccia, Fracesco Callea, Maria Rapicetta, Gamal Badr, Giovanni Rocchi
Journal: Journal of Hepatology (1997)
Histopathology of `fresh' human aortic valve allografts
Authors: J. B. Gavin, B. G. Barratt-Boyes, G. C. Hitchcock, P. B. Herdson
Journal: Thorax (1973)

<b>Gavin, J. B., Barratt-Boyes, B. G., Hitchcock, G. C., and Herdson, P. B. (1973).</b><i>Thorax</i>, <b>28,</b> 482-487. <b>Histopathology of `fresh9 human aortic valve allografts.</b> Six aortic valve allografts were studied histologically after having functioned in patients as aortic valve replacements for 14 to 442 weeks. The grafts initially had been collected under sterile conditions from cadavers and stored in Hanks9s balanced salt solution for 2 to 24 days before use. All grafts showed a cellular reaction along the host graft interface characterized by macrophages, lymphocytes, and organizing granulation tissue, and there was a progressive replacement of the donor aortic sleeve by host collagenous tissue. Sheaths of cellular, avascular host tissue extended from the margins of all grafts over their intimal surfaces and, in those which had been in place more than 36 weeks, this tissue had resulted in thickening of the proximal parts of one or more cusps. In one graft this thickening extended almost to the free margins of the cusps. While the leaflets of the graft at 14 weeks were virtually acellular, older grafts contained cellular areas with active fibroblasts in the proximal regions of the cusps as well as acellular regions which generally were more distally placed. Macrophages were always present along the interface between cellular and acellular areas. These observations indicate that there is a gradual replacement fibrosis of the graft by the host which proceeds in different grafts, and even different cusps in the same graft, at different rates.
PEI Conjugated Gold Nanoparticles: Efficient Gene Carriers with Visible Fluorescence
Authors: Huayu Tian, Zhaopei Guo, Jie Chen, Lin Lin, Jialiang Xia, Xuan Dong, Xuesi Chen
Journal: Advanced Healthcare Materials (2012)

Low molecular weight polyethyleneimines were conjugated onto gold nanoparticles to form Au-PEI conjugates. Au-PEI is the first reported gene carrier which has both high transfection efficiency and strong fluorescence. Au-PEI showed higher transfection efficiency and it can be used for bioimaging because it can be detected by confocal laser scanning microscopy and in vivo bioimaging system. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Irritants and asthma
Authors: Lidia Casas, Benoit Nemery
Journal: European Respiratory Journal (2014)

Asthma is a complex entity and one of the most common disorders in the world, affecting much of the workforce [1]. Asthma prevalence in children and adults has shown an increasing trend in the last decades [2], [3], which makes this disorder a major public health concern. Nevertheless, the mechanisms for the high incidence are not yet completely understood. In this regard, epidemiological studies focused on occupational asthma may contribute to unravelling the complexity of the disorder and the agents related to its onset and development.

Work-related asthma has been classified as comprising two main entities: sensitiser-induced asthma and irritant-induced asthma (IIA) [4]. The first involves a specific immunological response to a workplace sensitiser. These sensitisers are high-molecular-weight agents acting via the production of specific IgE antibodies or low-molecular-weight chemicals acting via other, hitherto less clarified immunological pathways [5]–[8]. The term IIA refers to asthma caused by exposure to agents that, when inhaled, act as respiratory irritants in the absence of sensitisation [9], [10]. In the 1980s, Brooks et al. [11] described reactive airway dysfunction syndrome. This diagnosis required very strict criteria that restricted the syndrome to the onset of asthma-like symptoms within 24 h after a single, very high exposure to an irritant agent. However, further studies suggested that repeated exposure to lower levels of irritants may also play a role in the onset …
Goalkeepers' positioning can reduce the uncertain of penalty shot direction in association football
Authors: L Vilar, L Santos, D Araújo, K Davids
Journal: British Journal of Sports Medicine (2011)

The ability to determine ball direction in advance is a key constraint on goalkeeping performance when facing penalty kicks in association football. In this communication we examined whether the positioning of the goalkeeper on the goal line might reduce the uncertainty of the shooting direction of the penalty kicker. Twelve male ( M =20, SD =2 y old) players (8 field players and 4 goalkeepers) performed 168 penalty kicks when facing goalkeepers who took up 21 different positions on the goal line (varied from the left post (−3.3 m) to the right post (3.3 m), manipulated in increments of 0.33 m). According to the shooting angle of the kicks, we divided the goal into 5 different areas: (1) −18° (left post) to −10.8°, (2) 10.8° to −3.6°, (3) −3.6° to 3.6°, (4) 3.6° to 10.8° and (5) 10.8° to 18° (right post). Outfield players aimed to score goals, while goalkeepers were asked to save the goal, maintaining their position until the ball was shot. Uncertainty of shooting direction was assessed by using Shannon's entropy measure for N=5 possible outcomes. Results showed that when goalkeepers were positioned at −0.66 m, uncertainty of shooting direction was higher (2.1) than when they were positioned at −0.33 m, 0 m, 0.66 m and 0.99 m (1.8). However, when goalkeepers were positioned at 0.33 m, uncertainty seemed to decrease to 1.5. These data suggest that the goalkeeper's positioning in the goal constrained the level of uncertainty in the direction of shooting in penalty kicks in association football. More precisely, it appears that, when the goalkeeper is positioned 0.33 m to the right of centre in the goal, this spatial location might increase the ability to determine ball direction in advance. Further research needs to examine the relation between the distance required for a goalkeeper to intercept the ball and the uncertainty in shooting direction.
Treatment of Malignant Carcinoid Tumors With Recombinant Interferon alfa-2b: Development of Neutralizing Interferon Antibodies and Possible Loss of Antitumor Activity
Authors: K. Oberg, G. Alm, A. Magnusson, G. Lundqvist, E. Theodorsson, L. Wide, E. Wilander
Journal: JNCI Journal of the National Cancer Institute (1989)

Twenty patients with malignant carci-noid tumors were treated for 6 months with recombinant interferon alfa-2b(IFN α-2b; Intron-A; Schering Corp., Bloomfield, NJ) at a mean dose of 5.9 megaunits three times per week. Eleven of the 20 patients (55%) had a <50% reduction of tumor markers (urinary5-hydroxyindoleacetic acid or plasmaneuropeptide K), showing objective tu-mor response. Six patients (30%) had stable disease with no significant change in tumor markers or tumor size, and three (15%) had progressive disease with an increase in tumor markers andsize. These results are similar to those reported earlier for treatment with natural leukocyte IFN in patients with carcinoid tumors. Only two patients (35%)had a slight reduction of tumor size after 6 months of treatment. Three patients developed neutralizing antibodies to IFN a-2b. Two of these patients initially showed an objective response, which lasted until IFN anti-bodies developed. In one of these patients, a change to human leukocyte IFN resulted in normalization of antibody titers within 3 months, and the patient had a second objective clinical response. There was no correlation between development of IFN antibod-ies and development of autoimmune phenomena such as increased titers of antinuclear antibodies or thyroid auto antibodies. IFN a-2b seems to be as potent as human leukocyte IFN in the treatment of patients with malignant carcinoid tumors, but it is important to recognize that antibodies neutralizing IFN may develop in some patients, with concomitant loss of antitumor effects. A change to natural leukocyte IFN might be beneficial in these pa-tients. [J Natl Cancer Inst 81:531-535,1989]
Rheumatoid arthritis, juvenile arthritis, iridocyclitis and the Epstein-Barr virus.
Authors: A J Gear, P J Venables, J M Edwards, R N Maini, B M Ansell
Journal: Annals of the Rheumatic Diseases (1986)

In order to examine the relation of Epstein-Barry virus (EBV) infection to chronic arthritis in children antibodies to EB virus capsid antigen (EBVCA) and rheumatoid arthritis nuclear antigen (RANA) were analysed in sera from 133 patients classified as juvenile rheumatoid arthritis (JRA) or pauciarticular, polyarticular, or systemic juvenile chronic arthritis. Except for an increased frequency in the systemic subgroup, the prevalence of antibodies to EBVCA and titres of anti-RANA antibodies was similar in patients and controls. These data do not support an aetiological role for EBV in chronic arthritis in children, including JRA, and suggest that the mechanisms which may account for the higher titres of anti-RANA antibodies in adult RA do not occur in children.
Aortic Origin of the Right Pulmonary Artery
Authors: SYLVIA P. GRIFFITHS, O. ROBERT LEVINE, DOROTHY H. ANDERSEN
Journal: Circulation (1962)

The clinical course and pathologic findings in three cases of anomalous origin of the right pulmonary artery from the ascending aorta are described. The malformation is characterized by (1) absent right branch of the pulmonary artery, (2) a single large vessel arising from the ascending aorta, entering the hilus of the lung and constituting its sole arterial blood supply, and (3) normal size and structure of the right lung. A review of the literature indicates the rarity of this lesion as an isolated anomaly; patent ductus arteriosus is the most frequently described additional defect. Histologic examination of the right and left lungs reveals bilateral and symmetrical pulmonary vascular changes, despite the difference in their arterial supply. Some pathophysiologic observations based on the necropsy findings in these cases are discussed. Early diagnosis and surgical correction are imperative, since this malformation may lead to irreversible congestive heart failure and death in infancy. Surgical repair may be accomplished by transplanting the anomalous right pulmonary artery from the aorta to the main pulmonary trunk.
Heme Oxygenase-1 and Carbon Monoxide in Vascular Pathobiology
Authors: Jozef Dulak, Jessy Deshane, Alicja Jozkowicz, Anupam Agarwal
Journal: Circulation (2008)

Angiogenesis involves the formation of new blood vessels and is critical for fundamental events such as development and repair after injury. Perturbances in angiogenesis contribute to the pathogenesis of diverse clinical conditions including cancer, complications of diabetes mellitus, ischemia/reperfusion injury of the heart and other organs, and preeclampsia, as well as a number of inflammatory disorders. Recent work has identified heme oxygenase-1 and its gaseous product, carbon monoxide, to possess potent proangiogenic properties in addition to well-recognized antiinflammatory, antioxidant, and antiapoptotic effects. Angiogenic factors, such as vascular endothelial growth factor and stromal cell-derived factor-1, mediate their proangiogenic effects through induction of heme oxygenase-1, making it an attractive target for therapeutic intervention. This review will provide an overview of the role of heme oxygenase-1 and carbon monoxide in angiogenesis.