tbuckley/cabot-search huggingface dataset:
The Mucosal Immune Response to Laryngopharyngeal Reflux
Authors: Louisa E. N. Rees, Laszlo Pazmany, Danuta Gutowska-Owsiak, Charlotte F. Inman, Anne Phillips, Christopher R. Stokes, Nikki Johnston, Jamie A. Koufman, Gregory Postma, Michael Bailey, Martin A. Birchall
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Laryngopharyngeal reflux (LPR) affects up to 20% of Western populations. Although individual morbidity is usually moderate, treatment costs are high and there are associations with other diseases, including laryngeal cancer. To date, there have been no studies of the mucosal immune response to this common inflammatory disease.To determine the mucosal immune response to LPR.We performed a prospective immunologic study of laryngeal biopsies from patients with LPR and control subjects (n = 12 and 11, respectively), and of primary laryngeal epithelial cells in vitro.Quantitative multiple-color immunofluorescence, using antibodies for lymphocytes (CD4, CD8, CD3, CD79, CD161), granulocytes (CD68, EMBP), monocytic cells (CD68, major histocompatibility complex [MHC] class II), and classical and nonclassical MHC (I, II, beta(2)-microglobulin, CD1d). Univariate and multivariate analysis and colocalization measurements were applied. There was an increase in percentage area of mucosal CD8(+) cells in the epithelium (P < 0.005), whereas other leukocyte and granulocyte antigens were unchanged. Although epithelial MHC class I and II expression was unchanged by reflux, expression of the nonclassical MHC molecule CD1d increased (P < 0.05, luminal layers). In vitro, laryngeal epithelial cells constitutively expressed CD1d. CD1d and MHC I expression were inversely related in all subjects, in a pattern which appears to be unique to the upper airway. Colocalization of natural killer T (NKT) cells with CD1d increased in patients (P < 0.01).These data indicate a role for the CD1d-NKT cell axis in response to LPR in humans. This represents a useful target for novel diagnostics and treatments in this common condition.
<i>In vitro</i> Activity of Bcr-Abl Inhibitors AMN107 and BMS-354825 against Clinically Relevant Imatinib-Resistant Abl Kinase Domain Mutants
Authors: Thomas O'Hare, Denise K. Walters, Eric P. Stoffregen, Taiping Jia, Paul W. Manley, Jürgen Mestan, Sandra W. Cowan-Jacob, Francis Y. Lee, Michael C. Heinrich, Michael W.N. Deininger, Brian J. Druker
Journal: Cancer Research (2005)

Abstract Imatinib, a Bcr-Abl tyrosine kinase inhibitor, is a highly effective therapy for patients with chronic myelogenous leukemia (CML). Despite durable responses in most chronic phase patients, relapses have been observed and are much more prevalent in patients with advanced disease. The most common mechanism of acquired imatinib resistance has been traced to Bcr-Abl kinase domain mutations with decreased imatinib sensitivity. Thus, alternate Bcr-Abl kinase inhibitors that have activity against imatinib-resistant mutants would be useful for patients who relapse on imatinib therapy. Two such Bcr-Abl inhibitors are currently being evaluated in clinical trials: the improved potency, selective Abl inhibitor AMN107 and the highly potent dual Src/Abl inhibitor BMS-354825. In the current article, we compared imatinib, AMN107, and BMS-354825 in cellular and biochemical assays against a panel of 16 kinase domain mutants representing &amp;gt;90% of clinical isolates. We report that AMN107 and BMS-354825 are 20-fold and 325-fold more potent than imatinib against cells expressing wild-type Bcr-Abl and that similar improvements are maintained for all imatinib-resistant mutants tested, with the exception of T315I. Thus, both inhibitors hold promise for treating imatinib-refractory CML.
Colour duplex sonography of finger arteries in vasculitis and in systemic sclerosis
Authors: W A Schmidt
Journal: Annals of the Rheumatic Diseases (2006)

Three patients-two with Wegener's granulomatosis and one with an overlap syndrome of rheumatoid vasculitis, systemic lupus erythematosus, and antiphospholipid syndrome-are described. All patients experienced a sudden onset of Raynaud's phenomenon or acrocyanosis when they had a flare of their disease.Ultrasonography (US) showed dark (hypoechoic) arteries without colour signals, resembling the US pattern of embolism. In contrast, US in patients with systemic sclerosis is entirely different, delineating a smaller artery lumen, reduced pulsation, and thickened, slightly hyperechoic artery walls.
The Spy1/RINGO Family Represents a Novel Mechanism Regulating Mammary Growth and Tumorigenesis
Authors: Azadeh Golipour, Dorothy Myers, Tiffany Seagroves, Daniel Murphy, Gerard I. Evan, Daniel J. Donoghue, Roger A. Moorehead, Lisa A. Porter
Journal: Cancer Research (2008)

Abstract Spy1A is a unique cell cycle activator known to mediate cell cycle progression and override the DNA damage response. This study focused on determining the role of this protein on postnatal mammary gland morphogenesis and neoplasia. Herein, we show that Spy1A levels are tightly regulated during mammary gland development and that ectopic expression stimulates precocious development and results in disrupted morphology of the gland. This follows the same trend as the oncogene c-Myc, and we show that Spy1A expression is regulated downstream of c-Myc signaling. Importantly, we show that overexpression of Spy1A accelerates tumorigenesis in vivo. Collectively, this work is the first report that the Spy1/RINGO family of proteins may play an essential role in regulating both normal and abnormal growth processes in the breast. [Cancer Res 2008;68(10):3591–600]
Detection of Cyclin D1 (bcl-1, PRAD1) Overexpression by a Simple Competitive Reverse Transcription-Polymerase Chain Reaction Assay in t(11; 14)(q13; q32)-Bearing B-Cell Malignancies and/or Mantle Cell Lymphoma
Authors: Kaoru Uchimaru, Toshiyasu Taniguchi, Miwa Yoshikawa, Shigetaka Asano, Andrew Arnold, Toshiro Fujita, Toru Motokura
Journal: Blood (1997)
Cooperative effects due to calcium binding by troponin and their consequences for contraction and relaxation of cardiac muscle under various conditions of mechanical loading.
Authors: None Izakov VYa, L B Katsnelson, F A Blyakhman, V S Markhasin, T F Shklyar
Journal: Circulation Research (1991)

A mathematical model for the regulation of mechanical activity in cardiac muscle has been developed based on a three-element rheological model of this muscle. The contractile element has been modeled taking into account the results of extensive mechanical tests that involved the recording of length-force and force-velocity relations and muscle responses to short-time deformations during various phases of the contraction-relaxation cycle. The best agreement between the experimental and the mathematical modeling results was obtained when a postulate stating two types of cooperativity to regulate the calcium binding by troponin was introduced into the model. Cooperativity of the first type is due to the dependence of the affinity of troponin C for Ca2+ on the concentration of myosin crossbridges in the vicinity of a given troponin C. Cooperativity of the second type assumes an increase in the affinity of a given troponin C for Ca2+ when the latter is bound by molecules neighboring troponin.
P290 Impact of a Combined Admission and Discharge COPD Care Bundle on Hospital Mortality and Readmission Rates
Authors: A Graham
Journal: Thorax (2012)

<h3>Background</h3> A care bundle is a group of evidence based interventions which if consistently delivered should improve outcomes. Published work (Thorax 2012) has demonstrated the impact of a COPD discharge bundle on hospital readmission rates. There is no published information on the use of bundles to address in-hospital mortality for COPD. <h3>Methods</h3> In April 2011 a care bundle for acute exacerbation of COPD (AECOPD) was introduced at both acute hospital sites in our Trust. The bundle content was printed on an adhesive sticker which was placed in the case notes. It consisted of a 7 point acute care section, completed on admission, and a 10 point discharge section completed prior to discharge. Multidisciplinary training and intranet guidance was provided to staff. Bundle use and compliance with each element was assessed quarterly through audit of 50 consecutive admissions. Hospital readmission rates and mortality were also reviewed. <h3>Results</h3> Audit was undertaken in October 2011, January 2012 and April 2012. Bundle stickers were reliably placed in the medical notes (&gt;80%). Delivery of all 7 admission bundle elements was high in each audit (&gt;75%), but compliance with the timings required fell during the ongoing audit (56%; 24%; 26%). Compliance was higher in patients admitted through A&amp;E compared to those admitted directly to MAU Compliance with all 10 discharge bundle elements initially improved but was not sustained (26%; 74%; 35%). Site specific comparison indicated that discharge bundle delivery was better with a hospital based respiratory specialist nursing "outreach" service, than with a community based "inreach" service. Overall compliance with all 17 bundle elements fell during the year (24%; 26%; 5%). Readmission rates compared to the previous financial year fell from 14.9% to 12.8%. Mortality rates also fell (figure). <h3>Conclusion</h3> Despite the lack of full compliance with the bundle, it was well used and improved outcomes were seen in terms of mortality and readmissions. It was felt that the bundle acted as a focus for improving knowledge and delivery of COPD care. Regular training and encouragement of staff will be required to sustain compliance with use of the bundle.
Epidermal growth factor receptor and related biomarkers evaluated by immunohistochemistry in patients with resected non-small cell lung cancer
Authors: Leila Antonangelo, Bruna Silva, Thayla Tuma, Lia Marcal, Milena Acencio, Edwin Parra, Ricardo Terra, Francisco Vargas, Vera Capelozzi
Journal: European Respiratory Journal (2013)

Purpose : It has been demonstrated that mutated EGFR and angiogenic biomarkers have relationship with clinical outcome in patients with non small cell lung cancer (NSCLC). The usefulness of mutation specific antibodies evaluated by IHC still remains to be determined. We evaluated if EGFR and angiogenic markers are related to prognosis and survival in a population of Brazilian patients with resected NSCLC.  Methods:  We used IHC to quantify EGFR, c-erb B2, VEGF, CD31, CD44 and Inhibitor of DNA binding proteins (Ids) 1-3 in tumor tissues from 92 patients with lung squamous cell carcinoma (SCC) or adenocarcinoma (Adeno). The impact of these markers was tested on patients’ survival until death.  Results : We observed increased amount of EGFR, c-erb B2, CD31, VEGF, CD44 and Id1-3 in the tumor tissue. Adeno showed higher expression of EGFR, c-erb B2, VEGF and CD44 than SCC. Tumors in N2 stage presented higher CD44 expression in the tumor stroma. Positive correlation was observed between tumor EGFR and c-erb B2 (R=0.40; p Conclusion : Abnormal expression of proteins related to tumor growth, progression and invasion can be demonstrated by IHC, mainly if we use mutation specific antibodies, supporting the idea that IHC may be promising in detecting biomarkers with impact on NSCLC patients’ survival.
Tumor-Associated Antigen Recognized by the 22-1-1 Monoclonal Antibody Encourages Colorectal Cancer Progression under the Scanty CD8+ T Cells
Authors: Taro Oshikiri, Masaki Miyamoto, Takayuki Morita, Miyoshi Fujita, Yuji Miyasaka, Naoto Senmaru, Hidehisa Yamada, Toshiyuki Takahashi, Shoichi Horita, Satoshi Kondo
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is a novel tumor-associated antigen. Although evidence suggests that RCAS1 suppresses immunity by inducing tumor-infiltrating lymphocyte (TIL) apoptosis, RCAS1 function in humans is controversial. RCAS1 overexpression leads to the generation of the Tn glycan antigen (N-acetyl-d-galactosamine, GalNAc) recognized by the 22-1-1 monoclonal antibody. The objective of this study is to examine Tn glycan antigen function in colorectal cancer and to determine its relationship to CD8+ T cells and prognosis. Experimental Design: Immunohistochemical analyses examined Tn expression in tumor cells and CD8 on TILs in 146 surgically resected colorectal cancer. Results: Of 146 samples, 68 tumors (47%) were Tn+; 72 tumors (49%) were CD8+. Using Cox multivariate analysis and the Kaplan-Meier method, Tn and CD8 positivity were determined to be mutually independent prognostic factors (P = 0.0266 and 0.0210, respectively). Tn+ patients with CD8+ TILs exhibited better survival than Tn+/CD8− patients (P = 0.0129). For CD8− patients, Tn positivity was associated with decreased survival from that seen in Tn− patients (P = 0.0097), suggesting that Tn exerts a function independent of CD8+ T cells in tumor progression. In all patients and cases with synchronous liver metastases (n = 29), the Tn+/CD8− survival rate was significantly lower than that seen for other groups (P = 0.0001 and 0.0063, respectively). The average number of liver metastases in Tn+/CD8− cases also increased (mean, 8.2 tumors; P = 0.0032). Multivariate analysis identified Tn+/CD8− status and Dukes' staging as independent prognostic factors (P = 0.0016 and &amp;lt;0.0001, respectively). Conclusions: Tn may encourage invasion and innidiation through a mechanism independent of CD8+ T cells. Thus, Tn+/CD8− status is a risk factor for multiple liver metastases development and an independent negative prognostic factor for colorectal cancer.
Abstract 1548: Genomic and molecular profiling of NSCLC formalin-fixed paraffin-embedded tumors
Authors: Dana S. Gaffney, Katherine Bell, Gabriela Martinez, Yashoda Rajpurohit, Jayaprakash Karkera, Christopher Moy, Suso Platero
Journal: Cancer Research (2014)

Abstract Non-Small Cell Lung Cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85% of all lung cancers worldwide. Standard therapy options include surgical resection followed by radiation and/or chemotherapy. More recently, analysis of the genomic profile of NSCLC has led to the development of molecularly targeted treatment strategies designed to enhance survival of select subsets of patients containing pre-determined genetic alterations, including gene mutations and aberrant gene expression profiles. In this study, we have developed a TaqMan-based approach to evaluate the genomic profile of 339 NSCLC FFPE tumors, consisting of 152 adenocarcinoma and 187 squamous cell carcinoma (SCC), stages I-IV. Using a custom qRT-PCR somatic mutation array, we have identified the frequencies of key mutations prevalent in NSCLC- associated genes, including EGFR: 5% SCC , 29% adenocarcinoma, cMET: 6% SCC, 4% adenocarcinoma, and KRAS: 3% SCC, 19% adenocarcinoma. Overall, these frequencies are concordant with previous reports. Additionally, we have evaluated the gene expression and IHC profiles of NSCLC-driver signaling pathways including EGFR, cMET and HGF. Various levels of expression for EGFR, cMET and HGF were observed across all samples, with a significant association detected between the presence of EGFR mutation and high EGFR expression in adenocarcinoma (p value = 0.0046). Overall, our findings represent a comprehensive catalog of common genetic aberrations with concurrent gene and protein expression profiles in NSCLC. Furthermore, this data provides insight into correlations observed across these molecular characteristics contributing to NSCLC tumor development. These insights can provide guidance for patient stratification and novel therapeutic strategies for select targeted therapies in NSCLC. Citation Format: Dana S. Gaffney, Katherine Bell, Gabriela Martinez, Yashoda Rajpurohit, Jayaprakash Karkera, Christopher Moy, Suso Platero. Genomic and molecular profiling of NSCLC formalin-fixed paraffin-embedded tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1548. doi:10.1158/1538-7445.AM2014-1548
Global Gene Expression Profiling in Whole-Blood Samples from Individuals Exposed to Metal Fumes
Authors: Zhaoxi Wang, Donna Neuburg, Cheng Li, Li Su, Jee Young Kim, Jiu Chiuan Chen, David C. Christiani
Journal: Environmental Health Perspectives (2004)

Accumulating evidence demonstrates that particulate air pollutants can cause both pulmonary and airway inflammation. However, few data show that particulates can induce systemic inflammatory responses. We conducted an exploratory study using microarray techniques to analyze whole-blood total RNA in boilermakers before and after occupational exposure to metal fumes. A self-controlled study design was used to overcome the problems of larger between-individual variation interferences with observations of relatively smaller changes caused by environmental exposure. Moreover, we incorporated the dichotomous data of absolute gene expression status in the microarray analyses. Compared with nonexposed controls, we observed that genes with altered expression in response to particulate exposure were clustered in biologic processes related to inflammatory response, oxidative stress, intracellular signal transduction, cell cycle, and programmed cell death. In particular, the preinflammatory cytokine interleukin 8 and one of its receptors, chemokine receptor 4, seemed to play important roles in early-stage response to heavy metal exposure and were down-regulated. Furthermore, most observed expression variations were from nonsmoking exposed individuals, suggesting that smoking profoundly affects whole-blood expression profiles. Our study is the first to demonstrate that with a paired sampling study design of pre- and postexposed individuals, small changes in gene expression profiling can be measured in whole-blood total RNA from a population-based study. This technique can be applied to evaluate the host response to other forms of environmental exposures.
Widespread Estrogen-Dependent Repression of microRNAs Involved in Breast Tumor Cell Growth
Authors: Gérard Maillot, Magali Lacroix-Triki, Sandra Pierredon, Lise Gratadou, Sabine Schmidt, Vladimir Bénès, Henri Roché, Florence Dalenc, Didier Auboeuf, Stefania Millevoi, Stéphan Vagner
Journal: Cancer Research (2009)

Altered expression of microRNAs (miRNA), an abundant class of small nonprotein-coding RNAs that mostly function as negative regulators of protein-coding gene expression, is common in cancer. Here, we analyze the regulation of miRNA expression in response to estrogen, a steroid hormone that is involved in the development and progression of breast carcinomas and that is acting via the estrogen receptors (ER) transcription factors. We set out to thoroughly describe miRNA expression, by using miRNA microarrays and real-time reverse transcription-PCR (RT-PCR) experiments, in various breast tumor cell lines in which estrogen signaling has been induced by 17beta-estradiol (E(2)). We show that the expression of a broad set of miRNAs decreases following E(2) treatment in an ER-dependent manner. We further show that enforced expression of several of the repressed miRNAs reduces E(2)-dependent cell growth, thus linking expression of specific miRNAs with estrogen-dependent cellular response. In addition, a transcriptome analysis revealed that the E(2)-repressed miR-26a and miR-181a regulate many genes associated with cell growth and proliferation, including the progesterone receptor gene, a key actor in estrogen signaling. Strikingly, miRNA expression is also regulated in breast cancers of women who had received antiestrogen neoadjuvant therapy. Overall, our data indicate that the extensive alterations in miRNA regulation upon estrogen signaling pathway play a key role in estrogen-dependent functions and highlight the utility of considering miRNA expression in the understanding of antiestrogen resistance of breast cancer.
Continuous stroke volume and cardiac output from intra-ventricular dimensions obtained with impedance catheter
Authors: J. BAAN, T. T A. JONG, P. L M KERKHOF, R. J MOENE, A. D VAN DIJK, E. T VAN DER VELDE, J. KOOPS
Journal: Cardiovascular Research (1981)

Journal Article Continuous stroke volume and cardiac output from intra-ventricular dimensions obtained with impedance catheter Get access JAN BAAN, JAN BAAN * From the Clinical Physiology Laboratory, Department of Paediatrics and Department of Cardiology, Leiden University Hospital, Leiden, Netherlands *Address for correspondence and reprint requests: Jan Baan, PhD. Clinical Physiology Laboratory, Department of Paediatrics, Leiden University Hospital. Rijnsburgerweg 10, 233.3 AA Leiden, Netherlands. Search for other works by this author on: Oxford Academic PubMed Google Scholar TJONG T AOUW JONG, TJONG T AOUW JONG From the Clinical Physiology Laboratory, Department of Paediatrics and Department of Cardiology, Leiden University Hospital, Leiden, Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar PETER L M KERKHOF, PETER L M KERKHOF From the Clinical Physiology Laboratory, Department of Paediatrics and Department of Cardiology, Leiden University Hospital, Leiden, Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar RUDOLF J MOENE, RUDOLF J MOENE From the Clinical Physiology Laboratory, Department of Paediatrics and Department of Cardiology, Leiden University Hospital, Leiden, Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar ARJAN D VAN DIJK, ARJAN D VAN DIJK From the Clinical Physiology Laboratory, Department of Paediatrics and Department of Cardiology, Leiden University Hospital, Leiden, Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar ENNO T VAN DER VELDE, ENNO T VAN DER VELDE From the Clinical Physiology Laboratory, Department of Paediatrics and Department of Cardiology, Leiden University Hospital, Leiden, Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar JAN KOOPS JAN KOOPS From the Clinical Physiology Laboratory, Department of Paediatrics and Department of Cardiology, Leiden University Hospital, Leiden, Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 15, Issue 6, June 1981, Pages 328–334, https://doi.org/10.1093/cvr/15.6.328 Published: 01 June 1981
A Multistep Photothermic‐Driven Drug Release System Using Wire‐Framed Au Nanobundles
Authors: Doyeon Bang, Taeksu Lee, Jihye Choi, Yeonji Park, Eunkyoung Kim, Yong‐Min Huh, Seungjoo Haam
Journal: Advanced Healthcare Materials (2014)

Here, wire‐framed Au nanobundles (WNBs), which consist of randomly oriented and mutually connected Au wires to form a bundle shape, are synthesized. In contrast to conventional nanoparticles (spheres, rods, cubes, and stars), which exhibit nanostructure only on the surface, cross‐sectional view image shows that WNBs have nanostructures in a whole volume. By using this specific property of WNBs, an externally controllable multistep photothermic‐driven drug release (PDR) system is demonstrated for in vivo cancer treatment. In contrast to conventional nanoparticles that encapsulate a drug on their surface, WNBs preserve the drug payload in the overall inner volume, providing a drug loading capacity sufficient for cancer therapy. An improved in vivo therapeutic efficacy of PDR therapy is also demonstrated by delivering sufficient amount of drugs to the target tumor region.