tbuckley/cabot-search huggingface dataset:
Polysaccharide intercellular adhesin or protein factors in biofilm accumulation of Staphylococcus epidermidis and Staphylococcus aureus isolated from prosthetic hip and knee joint infections
Authors: Holger Rohde, Eike C. Burandt, Nicolaus Siemssen, Lars Frommelt, Christoph Burdelski, Sabine Wurster, Stefanie Scherpe, Angharad P. Davies, Llinos G. Harris, Matthias A. Horstkotte, Johannes K.-M. Knobloch, Chandran Ragunath, Jeffrey B. Kaplan, Dietrich Mack
Journal: Biomaterials (2006)
Increased expression of nuclear factor- B in bronchial biopsies from smokers and patients with COPD
Authors: A. Di Stefano, G. Caramori, T. Oates, A. Capelli, M. Lusuardi, I. Gnemmi, F. Ioli, K.F. Chung, C.F. Donner, P.J. Barnes, I.M. Adcock
Journal: European Respiratory Journal (2002)

The expression of nuclear factor (NF)-κB is an indicator of cellular activation and of inflammatory mediator production. The aim of the present study was to characterise the expression and localisation of p65, the major subunit of NF-κB, in the bronchial mucosa of patients with chronic obstructive pulmonary disease (COPD), and to examine the relationship between p65 expression and disease status. Bronchial biopsies were obtained from 14 smokers with COPD, 17 smokers with normal lung function and 12 nonsmokers with normal lung function. The number of p65 positive (+) cells was quantified by immunohistochemistry and the expression of p65 in bronchial biopsies from the three groups was examined by Western blotting (WB). Smokers with normal lung function and patients with COPD had increased numbers of p65+ cells in the epithelium and increased p65 nuclear expression. In COPD patients the number of epithelial p65+ cells correlated with the degree of airflow limitation. WB analysis showed an increase in p65 in smokers with normal lung function and COPD patients (p&lt;0.05). Bronchial biopsies in smokers with normal lung function and chronic obstructive pulmonary disease patients show increased expression of p65 protein, predominantly in the bronchial epithelium. Disease severity is associated with an increased epithelial expression of nuclear factor-κB.
Decreased NKG2D Expression on CD8+ T Cell Is Involved in Immune Evasion in Patients with Gastric Cancer
Authors: Tomohiro Osaki, Hiroaki Saito, Toshiaki Yoshikawa, Sachiko Matsumoto, Shigeru Tatebe, Shunichi Tsujitani, Masahide Ikeguchi
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Some studies suggest that the immunoreceptor NKG2D expression on CD8+ T cells is down-regulated and this reduction may be involved in immune evasion in cancer patients. The present study was designed to investigate NKG2D expression on CD8+ T lymphocytes and its relationship to immune evasion in gastric cancer patients. Experimental Design: NKG2D expression on both circulating and tumor-infiltrating CD8+ T cells was evaluated by multicolor flow cytometry. Soluble MHC class I chain-related gene A (MICA) in the sera was quantitated by ELISA. Transwell experiments were carried out to determine the effect of cancer cells on NKG2D expression. Results: NKG2D expression on circulating CD8+ T cells was down-regulated and significantly correlated with IFN-γ production in gastric cancer patients (r = 0.68; P = 0.007). NKG2D expression was closely related to undifferentiated cancer (P = 0.021) as was the depth of invasion (P = 0.012). There was no difference in soluble MICA between gastric cancer patients and normal controls. NKG2D expression on CD8+ T cells was remarkably reduced in the tissue of gastric cancer compared with peripheral blood (P = 0.046). Complete removal of tumor by surgery restored NKG2D expression on CD8+ T cells (P = 0.0049). Transwell experiments showed that this down-regulation was induced by direct contact between cancer cells and CD8+ T cells and that soluble factors did not affect the NKG2D expression. This phenomenon was blocked by the addition of anti-MICA antibodies. Conclusions: Decreased NKG2D expression may be one of the key mechanisms responsible for immune evasion by tumors in gastric cancer.
Splenic Atrophy in Systemic Lupus Erythematosus
Authors: AILEEN M. DILLON
Journal: Annals of Internal Medicine (1982)

Five of 70 patients with systemic lupus erythematosus seen over a 5-year period had peripheral blood films suggestive of hyposplenism. Technetium-99m-sulphur colloid scans showed no splenic activity in three patients. One of these three patients, who had a spontaneous remission of persistent thrombocytopenia concurrent with the appearance of functional asplenia, had splenic atrophy shown by computed tomography; a second patient, who died of pneumococcal septicemia, was shown to have splenic atrophy with lymphocyte depletion at autopsy. The development of functional asplenia in the third patient has not, to date, had any obvious effect on her disease. In the two patients with normal scans, blood film findings returned to normal with treatment of the underlying disease. Polyvalent pneumococcal vaccine is recommended for patients with lupus erythematosus who have splenic atrophy.
Impact of Insulin Receptor Substrate-1 Genotypes on Platelet Reactivity and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease
Authors: Dominick J. Angiolillo, Esther Bernardo, Martina Zanoni, David Vivas, Piera Capranzano, Giovanni Malerba, Davide Capodanno, Paola Prandini, Alessandra Pasquali, Elisabetta Trabetti, Manel Sabaté, Pilar Jimenez-Quevedo, Jose L. Ferreiro, Masafumi Ueno, Theodore A. Bass, Pier Franco Pignatti, Antonio Fernandez-Ortiz, Carlos Macaya
Journal: Journal of the American College of Cardiology (2011)
Nonredundant Functions for Akt Isoforms in Astrocyte Growth and Gliomagenesis in an Orthotopic Transplantation Model
Authors: Raelene Endersby, Xiaoyan Zhu, Nissim Hay, David W. Ellison, Suzanne J. Baker
Journal: Cancer Research (2011)

The AKT family, comprising three highly homologous kinases, is an essential mediator of the PTEN/PI3K pathway, which is deregulated in many human cancers. A thorough understanding of the specific activities of each isoform in normal and disease tissues is lacking. We evaluated the role of each Akt isoform in gliomagenesis by using a model system driven by common glioma abnormalities, loss of function of p53 and Pten, and expression of EGFRvIII. Both Pten deletion and EGFRvIII expression accelerated the proliferation of p53-null primary murine astrocytes. All three Akt isoforms were expressed and phosphorylated in astrocytes, with significantly higher activation in Pten-null cells. Despite substantial compensation in many contexts when individual Akt isoforms were inhibited, isoform-specific effects were also identified. Specifically, loss of Akt1 or Akt2 decreased proliferation of Pten wild-type astrocytes, whereas combined loss of multiple isoforms was needed to inhibit proliferation of Pten-null astrocytes. In addition, Akt3 was required for anchorage-independent growth of transformed astrocytes and human glioma cells, and Akt3 loss inhibited invasion of transformed astrocytes. EGFRvIII expression transformed p53-null astrocytes with or without Pten deletion, causing rapid development of high-grade astrocytoma on intracranial transplantation. Furthermore, tumorigenesis of Pten;p53-null astrocytes expressing EGFRvIII was delayed by Akt1 loss and accelerated by Akt2 loss. Taken together, these results indicate context-dependent roles for individual Akt isoforms and suggest that there may be heterogeneous tumor response to isoform-specific inhibitors.
Tissue-Type Plasminogen Activator Modulates Inflammatory Responses and Renal Function in Ischemia Reperfusion Injury
Authors: Joris J T H Roelofs, Kasper M A Rouschop, Jaklien C Leemans, Nike Claessen, Anita M de Boer, Wilma M Frederiks, H Roger Lijnen, Jan J Weening, Sandrine Florquin
Journal: Journal of the American Society of Nephrology (2005)

Acute renal failure is often the result of ischemia-reperfusion (I/R) injury. Neutrophil influx is an important damaging event in I/R. Tissue-type plasminogen activator (tPA) not only is a major fibrinolytic agent but also is involved in inflammatory processes. A distinct upregulation of tPA after I/R, with de novo tPA production by proximal renal tubules, was found. For investigating the role of tPA in I/R, renal ischemia was induced in tPA-/- and wild-type (WT) mice by clamping both renal arteries for 35 min followed by reperfusion. Mice were killed 1, 5, and 10 d after reperfusion. After 1 d, tPA-/- mice displayed significantly less neutrophil influx into the interstitial area compared with WT mice. In addition, tPA-/- mice showed quicker recovery of renal function than WT mice. The protocol was repeated after injection of tPA-antisense oligonucleotides into WT mice, leading to even more explicit results: Antisense-treated mice showed less histologic damage, better renal function, and less neutrophil influx than control mice. Surprising, complement C3 concentration, levels of proinflammatory cytokines and chemokines, intercellular adhesion molecule-1 expression, and matrix metalloproteinase activity were similar in WT and tPA-/- mice. Plasmin activity levels in WT and tPA-/- kidneys were also comparable, indicating that tPA influences neutrophil influx into ischemic renal tissue independent from plasmin generation. This study shows that targeting tPA could be of therapeutic importance in treating I/R injury by diminishing neutrophil influx and preserving renal function.
Abstract CN4-1: Genome-wide discovery and clinical validation of pharmacogenomic markers for chemotherapy
Authors: R. Stephanie Huang
Journal: Clinical Cancer Research (2010)

Abstract Pharmacogenomics is emerging as an important component in facilitating both new drug development and in improving the utility of existing chemotherapeutic agents. However, the process of identifying these genetic variants is still evolving and there are a number of different approaches that can be employed. Typically, identification of the genetic contribution to drug response comes from clinical observations; but these clinical studies are limited by our inability to control environmental factors in vivo, the difficulty of manipulating the in vivo system to evaluate biological changes and the lack of single drug regimens in large oncology trials. Therefore, we have developed a whole genome, cell-based model for identifying genetic variation(s) important in chemotherapeutic agent-induced cytotoxicity using lymphoblastoid cell lines (LCLs) from samples included in the International HapMap project as well as extended CEPH pedigrees that have been subject to extensive genotyping for linkage mapping studies. We have identified that SNPs associated with chemotherapeutic sensitivity are enriched in expression quantitative trait locus (eQTLs). The presentation will include an overview of current cell-based models used in pharmacogenomic discovery, replication and translation into the clinical arena. As technology advances, a more comprehensive evaluation of the human genome, including the examination of rare SNPs, copy number variations, tandem repeats, epigenetic effects, will further improve our understanding of the relationship between genetics and drug response in cancers. Citation Information: Clin Cancer Res 2010;16(7 Suppl):CN4-1
Individual mRNA expression profiles reveal the effects of specific microRNAs
Authors: Amit Arora, David AC Simpson
Journal: Genome biology (2008)

MicroRNAs (miRNAs) are oligoribonucleotides with an important role in regulation of gene expression at the level of translation. Despite imperfect target complementarity, they can also significantly reduce mRNA levels. The validity of miRNA target gene predictions is difficult to assess at the protein level. We sought, therefore, to determine whether a general lowering of predicted target gene mRNA expression by endogenous miRNAs was detectable within microarray gene expression profiles.The target gene sets predicted for each miRNA were mapped onto known gene expression data from a range of tissues. Whether considering mean absolute target gene expression, rank sum tests or 'ranked ratios', many miRNAs with significantly reduced target gene expression corresponded to those known to be expressed in the cognate tissue. Expression levels of miRNAs with reduced target mRNA levels were higher than those of miRNAs with no detectable effect on mRNA expression. Analysis of microarray data gathered after artificial perturbation of expression of a specific miRNA confirmed the predicted increase or decrease in influence of the altered miRNA upon mRNA levels. Strongest associations were observed with targets predicted by TargetScan.We have demonstrated that the effect of a miRNA on its target mRNAs' levels can be measured within a single gene expression profile. This emphasizes the extent of this mode of regulation in vivo and confirms that many of the predicted miRNA-mRNA interactions are correct. The success of this approach has revealed the vast potential for extracting information about miRNA function from gene expression profiles.
Thrombin regulates PDGF expression in bovine glomerular endothelial cells.
Authors: G Grandaliano, G G Choudhury, E Poptic, K Woodruff, J L Barnes, H E Abboud
Journal: Journal of the American Society of Nephrology (1998)

The proteolytic enzyme thrombin is produced during activation of the coagulation pathway. Intraglomerular fibrin deposition and thrombosis are common pathologic features of several glomerular diseases, including transplant rejection. The effect of thrombin on platelet-derived growth factor (PDGF) production and DNA synthesis in well characterized bovine glomerular endothelial cells (G/endo) was studied. DNA synthesis was measured as the amount of [3H]thymidine incorporated into acid-insoluble material. PDGF released in the supernatant was measured by Western blotting and by a radioreceptor assay. PDGF mRNA expression was analyzed by solution hybridization, using human genomic PDGF B-chain (c-sis) and A-chain cDNA probes. G/endo constitutively secrete PDGF activity in serum-free medium. Thrombin stimulates PDGF production and increases the expression of mRNA that hybridizes with labeled B-chain but not A-chain probe, whereas epidermal growth factor and transforming growth factor-alpha stimulate the expression of PDGF A-chain mRNA. In addition, thrombin stimulates DNA synthesis with a peak effect at 24 h. Unlike endothelial cells from other microvascular beds, G/endo did not respond to any of the three PDGF isoforms BB, AB, or AA. These data demonstrate that bovine G/endo produce PDGF and that thrombin stimulates de novo synthesis of PDGF from these cells. Because mesangial, but not bovine, G/endo express PDGF receptors, PDGF released by G/endo is likely to modulate mesangial cell functions such as proliferation and matrix production by means of a paracrine mechanism.
Huntington's disease gene (IT15) is widely expressed in human and rat tissues
Authors: S.-H. Li, G. Schilling, W.S. Young, X.-. Li, R.L. Margolis, O.C. Stine, M.V. Wagster, M.H. Abbott, M.L. Franz, N.G. Ranen, S.E. Folstein, J.C. Hedreen, C.A. Ross
Journal: Neuron (1993)
Oseltamivir Ring Prophylaxis for Containment of 2009 H1N1 Influenza Outbreaks
Authors: Vernon J. Lee, Jonathan Yap, Alex R. Cook, Mark I. Chen, Joshua K. Tay, Boon Huan Tan, Jin Phang Loh, Seok Wei Chew, Wee Hong Koh, Raymond Lin, Lin Cui, Charlie W.H. Lee, Wing-Kin Sung, Christopher W. Wong, Martin L. Hibberd, Wee Lee Kang, Benjamin Seet, Paul A. Tambyah
Journal: New England Journal of Medicine (2010)

From June 22 through June 25, 2009, four outbreaks of infection with the pandemic influenza A (H1N1) virus occurred in Singapore military camps. We report the efficacy of ring chemoprophylaxis (geographically targeted containment by means of prophylaxis) with oseltamivir to control outbreaks of 2009 H1N1 influenza in semiclosed environments.
Metabolic therapies for heart disease: Fish for prevention and treatment of cardiac failure?
Authors: W STANLEY, F RECCHIA, I OKERE
Journal: Cardiovascular Research (2005)

See article by Takahashi et al.  [2]  (pages 213–223) in this issue. 

There are a myriad of structural and biochemical abnormalities associated with the failing heart, yet the hallmark of this syndrome is the inability to effectively transfer the chemical energy from foodstuffs to the mechanical energy of left ventricular ejection against aortic pressure. The causes and consequences of dysfunctional energy metabolism in heart failure are poorly understood; nevertheless, there is growing evidence to suggest that alterations in energy substrate metabolism contribute to cardiac hypertrophy, left ventricular remodeling, and systolic dysfunction. Present medical therapies for heart failure act via suppression of neurohormonal activation (e.g. β-adrenergic receptor antagonists, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, and aldosterone receptor antagonists), reducing volume overload (diuretics), or hemodynamic symptoms (inotropic agents). Despite optimal treatment with current drugs, most patients continue to deteriorate, and the prognosis remains poor; thus, additional effective therapies are needed that act independent of … 

*Corresponding author. Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4970, USA. Tel.: +1 216 368 5585; fax: +1 216 368 3952. Email address: wcs4{at}case.edu
Preventive effect of erythromycin on experimental bleomycin-induced acute lung injury in rats
Authors: A. Azuma, T. Furuta, T. Enomoto, Y. Hashimoto, K. Uematsu, N. Nukariya, A. Murata, S. Kudoh
Journal: Thorax (1998)

<h3>BACKGROUND</h3> Erythromycin has been reported to have an inhibitory effect on chronic inflammatory airway disease and chronic infiltration of neutrophils into the airway. Bleomycin (BLM) often induces interstitial lung fibrosis following acute lung injury. A study was undertaken to investigate the effects of erythromycin (EM) on experimental bleomycin-induced acute lung injury in rats. <h3>METHODS</h3> Bleomycin-induced lung injury was assessed by light microscopic examination, measurement of neutrophil elastase activity and of the interleukin 8 (IL-8) content in bronchoalveolar lavage (BAL) fluid. The potential inhibitory effect of erythromycin was assessed by overall comparison of erythromycin untreated (BLM alone), concurrently treated (BLM + EM), and pretreated (BLM + pre-EM) groups. <h3>RESULTS</h3> The neutrophil count and concentration of neutrophil-derived elastase in BAL fluid were significantly different in the three groups. The morphological changes of lung injury were also less extensive in rats pretreated with erythromycin. However, these protective effects were not marked in the group concurrently treated with erythromycin. Moreover, the concentration of IL-8 in the BAL fluid tended to be less in the erythromycin treated groups; however, there were no significant differences between the bleomycin-treated groups. <h3>CONCLUSION</h3> Erythromycin exhibits a prophylactic effect on acute lung injury induced by intratracheal administration of bleomycin, which is possibly associated with a downregulation of neutrophil-derived elastase.
Randomized Adjuvant Trial of Tamoxifen and Goserelin Versus Cyclophosphamide, Methotrexate, and Fluorouracil: Evidence for the Superiority of Treatment With Endocrine Blockade in Premenopausal Patients With Hormone-Responsive Breast Cancer—Austrian Breast and Colorectal Cancer Study Group Trial 5
Authors: Raimund Jakesz, Hubert Hausmaninger, Ernst Kubista, Michael Gnant, Christian Menzel, Thomas Bauernhofer, Michael Seifert, Karin Haider, Brigitte Mlineritsch, Peter Steindorfer, Werner Kwasny, Michael Fridrik, Guenther Steger, Viktor Wette, Hellmut Samonigg
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Effective adjuvant treatment modalities in premenopausal breast cancer patients today include chemotherapy, ovariectomy, and tamoxifen administration. The purpose of Austrian Breast and Colorectal Cancer Study Group Trial 5 was to compare the efficacy of a combination endocrine treatment with standard chemotherapy. PATIENTS AND METHODS: Assessable trial subjects (N = 1,034) presenting with hormone-responsive disease were randomized to receive either 3 years of goserelin plus 5 years of tamoxifen or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Stratification criteria included tumor stage and grade, number of involved nodes, type of surgery, and steroid hormone receptor content. Relapse-free survival (RFS) was defined as time from randomization to first relapse, local recurrence, or contralateral incidence, and overall survival (OS) as time to date of death. RESULTS: With a 60-month median follow-up, 17.2% of patients in the endocrine group and 20.8% undergoing chemotherapy developed relapses. Local recurrences emerged in 4.7% and 8.0%, respectively. RFS and local recurrence-free survival differed significantly in favor of endocrine therapy (P = .037 and P = .015), with a similar trend observed in OS (P = .195). CONCLUSION: Overall, our data suggest that the goserelin-tamoxifen combination is significantly more effective than CMF in the adjuvant treatment of premenopausal patients with stage I and II breast cancer.
Interactions between Leukotrienes and Other Inflammatory Mediators/Modulators in the Microvasculature
Authors: PER HEDQVIST, NARINDER GAUTAM, LENNART LINDBOM
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Throughout its many years as a powerful smooth muscle stimulant of unknown chemical structure, slow-reacting substance of anaphylaxis (SRS-A) remained an intriguing entity, possibly implicated as a mediator of hypersensitivity reactions, in particular those concerned with allergic asthma. Elucidation of the chemical structure of SRS-A, and the realization that it was not a single substance but rather a mixture of interrelated leukotrienes (LTs), necessitated reappraisal of earlier data about the effects of SRS-A in pulmonary tissue. Furthermore, as the LT family grew larger, interest turned also to other tissues and organ systems, with the ultimate goal to disclose specific targets for the various LTs. It is now generally accepted that the LTs collectively provoke contraction of vascular and nonvascular smooth muscle, enhanced vascular permeability, and accumulation and activation of leukocytes. The LTs often operate with a potency that far exceeds that of traditional autacoids, and they have obvious key targets of action within the pulmonary and cardiovascular systems. It has been conclusively documented that LTs are important mediators in bronchial asthma, and data are accumulating that they are involved in a number of other disease states, such as rheumatoid arthritis, inflammatory bowel disease, glomerulonephritis, and cardiac disorders. This article summarizes the microvascular actions of LTs formed via the 5-lipoxygenase pathway, and the interplay of these LTs and some other eicosanoids and histamine in the process of inflammation.