tbuckley/cabot-search huggingface dataset:
Resolvins
Authors: Charles N. Serhan, Song Hong, Karsten Gronert, Sean P. Colgan, Pallavi R. Devchand, Gudrun Mirick, Rose-Laure Moussignac
Journal: The Journal of Experimental Medicine (2002)

Aspirin (ASA) is unique among current therapies because it acetylates cyclooxygenase (COX)-2 enabling the biosynthesis of R-containing precursors of endogenous antiinflammatory mediators. Here, we report that lipidomic analysis of exudates obtained in the resolution phase from mice treated with ASA and docosahexaenoic acid (DHA) (C22:6) produce a novel family of bioactive 17R-hydroxy-containing di- and tri-hydroxy-docosanoids termed resolvins. Murine brain treated with aspirin produced endogenous 17R-hydroxydocosahexaenoic acid as did human microglial cells. Human COX-2 converted DHA to 13-hydroxy-DHA that switched with ASA to 17R-HDHA that also proved a major route in hypoxic endothelial cells. Human neutrophils transformed COX-2-ASA–derived 17R-hydroxy-DHA into two sets of novel di- and trihydroxy products; one initiated via oxygenation at carbon 7 and the other at carbon 4. These compounds inhibited (IC50 ∼50 pM) microglial cell cytokine expression and in vivo dermal inflammation and peritonitis at ng doses, reducing 40–80% leukocytic exudates. These results indicate that exudates, vascular, leukocytes and neural cells treated with aspirin convert DHA to novel 17R-hydroxy series of docosanoids that are potent regulators. These biosynthetic pathways utilize omega-3 DHA and EPA during multicellular events in resolution to produce a family of protective compounds, i.e., resolvins, that enhance proresolution status.
Signature of circulating microRNAs in osteoarthritis
Authors: Christian Beyer, Anna Zampetaki, Neng-Yu Lin, Arnd Kleyer, Carlo Perricone, Annamaria Iagnocco, Alfiya Distler, Sarah R Langley, Kolja Gelse, Stefan Sesselmann, Rolando Lorenzini, Andreas Niemeier, Bernd Swoboda, Jörg H W Distler, Peter Santer, Georg Egger, Johann Willeit, Manuel Mayr, Georg Schett, Stefan Kiechl
Journal: Annals of the Rheumatic Diseases (2014)

Osteoarthritis is the most common form of arthritis and a major socioeconomic burden. Our study is the first to explore the association between serum microRNA levels and the development of severe osteoarthritis of the knee and hip joint in the general population.
CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells.
Authors: M F Krummel, J P Allison
Journal: The Journal of Experimental Medicine (1996)

While interactions between CD28 and members of the B7 family costimulate and enhance T cell responses, recent evidence indicates that the CD28 homologue CTLA-4 plays a downregulatory role. The mechanism by which this occurs is not clear, but it has been suggested that CTLA-4 terminates ongoing responses of activated T cells, perhaps by induction of apoptosis. Here we demonstrate that CTLA-4 engagement by antibody cross-linking or binding to B7 inhibits proliferation and accumulation of the primary T cell growth factor, IL-2, by cells stimulated with anti-CD3 and anti-CD28. This inhibition is not a result of enhanced cell death. Rather it appears to result from restriction of transition from the G1 to the S phase of the cell cycle. Our observation that upregulation of both the IL-2R alpha chain and the CD69 activation antigen are inhibited by CTLA-4 engagement supplies further evidence that CTLA-4 restricts the progression of T cells to an activated state. Together this data demonstrates that CTLA-4 can regulate T cell activation in the absence of induction of apoptotic cell death.
Expression of cancer-testis antigen in patients with non-small cell lung cancer and its clinical relevance
Authors: Xin-Feng Chen, Meng Wang, Dong-Li Yue, Jin-Yan Liu, Lan Huang, Feng Li, Song Zhao, Yu Qi, Wei Hu, Xiang-Nan Li, Yi Zhang
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Lung cancer is the most common cause of cancer-related mortality worldwide. Survival rates after non-small cell lung cancer (NSCLC) diagnosis still remain poor, despite standardization of surgery and adjuvant treatment. Cancer testis (CT) antigens as targets for immunotherapy in
The Role of the Thymus in Polyoma Virus Infection&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Mitsuo Kodama, George E. Moore
Journal: JNCI Journal of the National Cancer Institute (1963)

To clarify the host-virus relationship in polyoma virus infection, virus from a single culture pool was inoculated intravenously into AKR and C3H mice and F1 hybrids within 24 hours after birth. Half the mice were thymectomized 2 weeks later. A high sensitivity of AKR mice to polyoma virus infection was shown in terms of the cumulative mortality, and of the incidence and mean latent period of parotid tumor growth in animals that survived more than 60 days. Thymectomy delayed significantly the death of infected mice in the AKR strain, but not in the C3H strain. The incidence and latency of parotid tumors were not affected by thymectomy in these strains of mice. High sensitivity to polyoma virus, the ameliorating effect of thymectomy, and predisposition for leukemia were observed in F1 hybrids whose mothers were AKR mice, but not in those whose mothers were C3H mice. It is concluded that there is a close correlation between the predisposition of AKR mice for leukemia and their sensitivity to polyoma virus infection, and that the thymus gland is partly, if not entirely, responsible for the high sensitivity. The incidence of leukemia was not significantly affected by the presence of polyoma virus infection.
The diagnosis and management of anaphylaxis practice parameter: 2010 Update
Authors: Phillip Lieberman, Richard A Nicklas, John Oppenheimer, Stephen F Kemp, David M Lang, David I Bernstein, Jonathan A Bernstein, A Wesley Burks, Anna M Feldweg, Jordan N Fink, Paul A Greenberger, David B K Golden, John M James, Stephen F Kemp, Dennis K Ledford, Phillip Lieberman, Albert L Sheffer, David I Bernstein, Joann Blessing-Moore, Linda Cox, David A Khan, David Lang, Richard A Nicklas, John Oppenheimer, Jay M Portnoy, Christopher Randolph, Diane E Schuller, Sheldon L Spector, Stephen Tilles, Dana Wallace
Journal: Journal of Allergy and Clinical Immunology (2010)
Mechanism of Induction of Ovarian Tumors in the Mouse by 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene. IV. Uptake and Retention of&lt;sup&gt;14&lt;/sup&gt;C-DMBA by Mouse and Rat Tissues&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J. W. Jull, P. H. Jellinck
Journal: JNCI Journal of the National Cancer Institute (1968)

14C-7,12-Dimethylbenz[a]anthracene was taken up by all tissues of the rat and the mouse assayed at intervals after the intravenous injection of a suspension of the carcinogen. Initially the tissues differed considerably, the adrenals having the highest activity. But by 24 hours the levels did not vary greatly between various tissues in the mouse. Mouse ovaries exposed to the carcinogen in organ culture for 4 or more hours absorbed more of the carcinogen than was found 15 minutes after intravenous injection. This activity was lost more rapidly after subcutaneous transplantation into ovariectomized mice than after transfer of the ovaries to fresh organ culture medium not containing the carcinogen.
Paternally Inherited Submicroscopic Duplication at 11p15.5 Implicates Insulin-like Growth Factor II in Overgrowth and Wilms' Tumorigenesis
Authors: Elizabeth M. Algar, Luke St. Heaps, Artur Darmanian, Vinod Dagar, Dirk Prawitt, Greg B. Peters, Felicity Collins
Journal: Cancer Research (2007)

Loss of imprinting at insulin-like growth factor II (IGFII), in association with H19 silencing, has been described previously in a subgroup of Beckwith-Wiedemann syndrome (BWS) patients who have an elevated risk for Wilms' tumor. An equivalent somatic mutation occurs in sporadic Wilms' tumor. We describe a family with overgrowth in three generations and Wilms' tumor in two generations, with paternal inheritance of a cis-duplication at 11p15.5 spanning the BWS IC1 region and including H19, IGFII, INS, and TH. The duplicated region was below the limit of detection by high-resolution karyotyping and fluorescence in situ hybridization, has a predicted minimum size of 400 kb, and was confirmed by genotyping and gene-dosage analysis on a CytoChip comparative genomic hybridization bacterial artificial chromosome array. IGFII is the only known paternally expressed oncogene mapping within the duplicated region and our findings directly implicate IGFII in Wilms' tumorigenesis and add to the mutation spectrum that increases the effective dose of IGFII. Furthermore, this study raises the possibility that sporadic cases of overgrowth and Wilms' tumor, presenting with apparent gain of methylation at IC1, may be explained by submicroscopic paternal duplications. This finding has important implications for determining the transmission risk in these disorders.
Effectiveness of adenotonsillectomy in children with mild symptoms of throat infections or adenotonsillar hypertrophy: open, randomised controlled trial
Authors: Birgit K van Staaij, Emma H van den Akker, Maroeska M Rovers, Gerrit Jan Hordijk, Arno W Hoes, Anne G M Schilder
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To assess the effectiveness of adenotonsillectomy in children with mild symptoms of throat infections or adenotonsillar hypertrophy. <b>Design</b> Open, randomised controlled trial. <b>Setting</b> 21 general hospitals and three academic centres in the Netherlands. <b>Participants</b> 300 children aged 2-8 years requiring adenotonsillectomy. <b>Intervention</b> Adenotonsillectomy compared with watchful waiting. <b>Main outcome measures</b> Episodes of fever, throat infections, upper respiratory tract infections, and health related quality of life. <b>Results</b> During the median follow up period of 22 months, children in the adenotonsillectomy group had 2.97 episodes of fever per person year compared with 3.18 in the watchful waiting group (difference −0.21, 95% confidence interval −0.54 to 0.12), 0.56 throat infections per person year compared with 0.77 (−0.21, −0.36 to −0.06), and 5.47 upper respiratory tract infections per person year compared with 6.00 (−0.53, −0.97 to −0.08). No clinically relevant differences were found for health related quality of life. Adenotonsillectomy was more effective in children with a history of three to six throat infections than in those with none to two. 12 children had complications related to surgery. <b>Conclusion</b> Adenotonsillectomy has no major clinical benefits over watchful waiting in children with mild symptoms of throat infections or adenotonsillar hypertrophy.
Ultrastructural and immunohistochemical findings in Alport's syndrome
Authors: G Mazzucco, P Barsotti, A O Muda, M Fortunato, M Mihatsch, L Torri-Tarelli, A Renieri, T Faraggiana, M De Marchi, G Monga
Journal: Journal of the American Society of Nephrology (1998)

A total of 108 patients affected by Alport's syndrome, taken from 97 families, were enrolled in a genetic and ultrastructural study. Sixty-four families (75 patients) were X-linked, seven autosomal recessive, two autosomal dominant, five uninterpretable, and 19 sporadic. The ultrastructural features were consistent with Alport's syndrome in 66, doubtful in 20, and not significant for Alport's syndrome in 22 patients in the X-linked, sporadic, and genetically uninterpretable groups (without significant differences), as well as in the autosomal group. Mutations of the COL4A5 gene were present in 36 patients in the first three groups, without significant differences. More severe mutations were more frequently present in patients with an ultrastructural pattern consistent with Alport's syndrome. Nevertheless, there seems to be no strict correlation between mutation and ultrastructure, because a major rearrangement was found in a patient with no significant lesions, and different morphologic patterns were detected in patients Belonging to the same family. Immunohistochemical investigation into 24 patients for alpha (IV) chains showed that both alpha 3(IV) and alpha 5(IV) were lacking in the glomerular basement membrane of 13 patients (five with mutations) and were expressed in another six (three with mutations and one in the autosomal group). On the contrary, in this study the retained expression of alpha 3(IV) chain was found, despite the lack of alpha 5(IV) in the glomerular basement membrane of five patients (two with mutation). These different patterns could be related to both the type and severity of the COL4A5 mutations. All of the ultrastructural patterns were identified in all three immunohistochemical groups. Ultrastructural features and alpha 5(IV) chain production, even if an expression of a genetic mutation, do not strictly correlate. The combined use of analysis of collagen expression and electron microscopy made it possible to diagnose Alport's syndrome in 92% of the cohort, and therefore this approach is advisable. A multidisciplinary approach is recommended in the study of Alport's syndrome in an attempt to achieve a better diagnostic definition of and insight into the pathogenetic mechanisms.
Causes of pneumonia presenting to a district general hospital.
Authors: R J White, A D Blainey, K J Harrison, S K Clarke
Journal: Thorax (1981)

The incidence of bacterial, viral, mycoplasma, and rickettsial infections has been assessed prospectively in 210 adult patients with pneumonia who presented to a district hospital over a six-year period. One hundred and thirteen infective agents were detected in 103 patients. The agent most frequently detected was Mycoplasma pneumoniae which accounted for 30 infections. A bacterial pathogen was found in 43 patients. Streptococcus pneumoniae was the most common of these (24 patients); Staphylococcus aureus (eight), Haemophilus influenzae (four), Klebsiella spp (three), and Legionella pneumophila (three) were all less common. Chlamydial or rickettsial infections (Psittacosis or Q fever) were detected in nine patients. Viral infections were found in 31 patients (22 influenza A, four influenza B, two parainfluenza, and three respiratory syncytial virus). There were 10 patients in whom more than one pathogen was identified. In 107 patients no pathogens could be identified. Seventy-five per cent of these patients had either received antibiotics before entering hospital, or were unable to produce any sputum for culture. The incidence of bacterial pneumonia has probably therefore been underestimated. Nevertheless this survey does emphasise the importance of M pneumoniae as a pathogen in patients with pneumonia presenting to hospital.
Downregulation of miR-342 is associated with tamoxifen resistant breast tumors
Authors: Diana M Cittelly, Partha M Das, Nicole S Spoelstra, Susan M Edgerton, Jennifer K Richer, Ann D Thor, Frank E Jones
Journal: Molecular Cancer (2010)

Abstract Background Tumor resistance to the selective estrogen receptor modulator tamoxifen remains a serious clinical problem especially in patients with tumors that also overexpress HER2. We have recently demonstrated that the clinically important isoform of HER2, HERΔ16, promotes therapeutically refractory breast cancer including resistance to endocrine therapy. Likewise additional breast tumor cell models of tamoxifen resistance have been developed that do not involve HER2 overexpression. However, a unifying molecular mechanism of tamoxifen resistance has remained elusive. Results Here we analyzed multiple cell models of tamoxifen resistance derived from MCF-7 cells to examine the influence of microRNAs (miRNAs) on tamoxifen resistance. We compared miRNA expression profiles of tamoxifen sensitive MCF-7 cells and tamoxifen resistant MCF-7/HER2Δ16 cells. We observed significant and dramatic downregulation of miR-342 in the MCF-7/HER2Δ16 cell line as well as the HER2 negative but tamoxifen resistant MCF-7 variants TAMR1 and LCC2. Restoring miR-342 expression in the MCF-7/HER2Δ16 and TAMR1 cell lines sensitized these cells to tamoxifen-induced apoptosis with a dramatic reduction in cell growth. Expression of miR-342 was also reduced in a panel of tamoxifen refractory human breast tumors, underscoring the potential clinical importance of miR-342 downregulation. Towards the goal of identifying direct and indirect targets of miR-342 we restored miR-342 expression in MCF-7/HER2Δ16 cells and analyzed changes in global gene expression by microarray. The impact of miR-342 on gene expression in MCF-7/HER2Δ16 cells was not limited to miR-342 in silica predicted targets. Ingenuity Pathways Analysis of the dataset revealed a significant influence of miR-342 on multiple tumor cell cycle regulators. Conclusions Our findings suggest that miR-342 regulates tamoxifen response in breast tumor cell lines and our clinical data indicates a trend towards reduced miR-342 expression and tamoxifen resistance. In addition, our results suggest that miR-342 regulates expression of genes involved in tamoxifen mediated tumor cell apoptosis and cell cycle progression. Restoring miR-342 expression may represent a novel therapeutic approach to sensitizing and suppressing the growth of tamoxifen refractory breast tumors.
Multicenter, Phase I, Dose-Escalation Trial of Lenalidomide Plus Bortezomib for Relapsed and Relapsed/Refractory Multiple Myeloma
Authors: Paul G. Richardson, Edie Weller, Sundar Jagannath, David E. Avigan, Melissa Alsina, Robert L. Schlossman, Amitabha Mazumder, Nikhil C. Munshi, Irene M. Ghobrial, Deborah Doss, Diane L. Warren, Laura E. Lunde, Mary McKenney, Carol Delaney, Constantine S. Mitsiades, Teru Hideshima, William Dalton, Robert Knight, Dixie-Lee Esseltine, Kenneth C. Anderson
Journal: Journal of Clinical Oncology (2009)

Lenalidomide and bortezomib are active in relapsed and relapsed/refractory multiple myeloma (MM). In preclinical studies, lenalidomide sensitized MM cells to bortezomib and dexamethasone. This phase I, dose-escalation study (ie, NCT00153933) evaluated safety and determined the maximum-tolerated dose (MTD) of lenalidomide plus bortezomib in patients with relapsed or with relapsed and refractory MM.
Comparison of different GC-IMS-devices for measurement of volatile biomarkers (VOC)
Authors: Gunther Becher, Roman Purkhart, Anne Hillmann, Rolf Graupner, Schueler Werner
Journal: European Respiratory Journal (2014)

Introduction  The Ion Mobility Spectrometry (IMS) is a highly sensitive analytical method for detection of volatile organic compounds (VOCs) in air. Available studies were typically done with one device in mono-centric studies only. The aim of the study was the comparison of different devices.  Methods:  The headspaces of in vitro cultures of two strains of  mycobacterium avium  were measured with a GC-differential-ion-mobility-spectrometry (DMS-SIONEX) as well as with a GC-IMS Prototype (GC-IMS) 1 week after inoculation. Pure breeding grounds were measured as control. Both devices show spectra with comparable numbers of peaks. The spectra were analyzed by a statistical program based on cluster analysis.  Results  With both devices was possible a significant differentiation between control and the bacterial growth. Each cluster represents the same peaks, e.g. detected metabolite, in the different measurements. Fig. 1 shows clusters for differentiation between control (left) and strain 1 (middle) and strain 2 (right) for both devices.  Discussion  With both devices the differentiation between breeding ground and bacterial growth was possible with a sensitivity and specifity of 100%. The detected clusters should be verified between the devices. Differentiation between two devices will be helpful for evaluation of peaks. GC-IMS may be a more rapid tool for detection of bacterial growth in vitro than traditional methods.
Approaches to Treatment of Pre-Diabetes and Obesity and Promising New Approaches to Type 2 Diabetes
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2008)

Perspectives on the News commentaries are part of a free monthly CME activity. The Mount Sinai School of Medicine, New York, New York, designates this activity for 2.0 AMA PRA Category 1 credits. If you wish to participate, review this article and visit www.diabetes.procampus.net to complete a posttest and receive a certificate. The Mount Sinai School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians .

This article is based on presentations at the Tulane University Diabetes Update on 8 December 2007 in New Orleans, Louisiana; at the Mount Sinai Medical Center Diabetes Grand Rounds in New York, New York, on 6 December 2007; and at the American Diabetes Association's 55th Annual Advanced Postgraduate Course held 1–3 February 2008 in San Francisco, California. These lectures, addressing differing views of various speakers on various aspects of diabetes prevention, obesity, and new treatments for type 2 diabetes, are available online at http://professional.diabetes.org.

Richard Bergenstal (Minneapolis, MN) reviewed approaches to treatment of pre-diabetes at the American Diabetes Association Postgraduate Course. The number of individuals with diabetes worldwide is projected to increase to 333 million by 2025, and the annual cost of diabetes in the U.S. today has reached $174 billion (1). The burden of complications among diabetic individuals aged >65 years in the U.S. includes doubling of the rates of myocardial infarction and congestive heart failure (2). Bergenstal reviewed current guidelines for using elevated fasting and 2-h glucose, as well as the growing use of A1C, in the assessment of the pre-diabetic state. The presence of both impaired fasting glucose (IFG) (≥100 mg/dl) and impaired glucose tolerance (IGT) (blood glucose 2 h after 75-g oral glucose ≥140 mg/dl) doubles the risk of progression to diabetes. Insulin secretory defects are seen in …
Impact Of Posaconazole Prophylaxis On Invasive Fungal Infection During Acute Myeloid Leukemia Induction Therapy: Correlation With Posaconazole Serum Levels
Authors: Chiara Cattaneo, Erika Borlenghi, Annafranca Panzali, Francesca Antoniazzi, Marta Petullà, Francesca Schieppati, Elisa Cerqui, Chiara Pagani, Alessandro Re, Giuseppe Rossi
Journal: Blood (2013)
Effects of Budesonide and Formoterol on NF- κ B, Adhesion Molecules, and Cytokines in Asthma
Authors: SUSAN J. WILSON, ANNIKA WALLIN, GIOVANNI DELLA-CIOPPA, THOMAS SANDSTRÖM, STEPHEN T. HOLGATE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The asthmatic inflammatory response can be attenuated by corticosteroids and in part by β2-agonists. We investigated if these effects are accompanied by a downregulation in nuclear factor kappa B (NF- κ B), a transcription factor regulating many of the cytokine and adhesion molecule genes expressed in allergic inflammation. Bronchial biopsies were taken before and after 8 wk treatment with formoterol, budesonide, or placebo from atopic asthmatics. Biopsies were processed into glycol methacrylate and stained immunohistochemically for eosinophils (as an index of inflammation), activated and total NF- κ B, adhesion molecules, and cytokines. After budesonide treatment there was a significant decrease in the number of submucosal cells staining for total NF- κ B, granulocyte macrophage colony–stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF- α ), accompanied by a significant decrease in mucosal eosinophils and expression of vascular cell adhesion molecule-1 (VCAM-1) in the endothelium and interleukin-8 (IL-8) in the epithelium. After formoterol treatment there was a significant decrease in eosinophils and the epithelial expression of activated NF- κ B, but these changes were not accompanied by reduced immunoreactivity for adhesion molecules or cytokines. We conclude that at least some of the therapeutic efficacy of inhaled corticosteroids is mediated through inhibition of NF- κ B-regulated gene expression, whereas the reduction in airway eosinophilia by long-acting β2-agonists probably operates through alternative pathways.Keywords: budesonide; formoterol; NF-κB; immunohistochemistry; asthma