tbuckley/cabot-search huggingface dataset:
The IL-4/STAT6 signaling axis establishes a conserved microRNA signature in human and mouse macrophages regulating cell survival via miR-342-3p
Authors: Zsolt Czimmerer, Tamas Varga, Mate Kiss, Cesaré Ovando Vázquez, Quang Minh Doan-Xuan, Dominik Rückerl, Sudhir Gopal Tattikota, Xin Yan, Zsuzsanna S. Nagy, Bence Daniel, Szilard Poliska, Attila Horvath, Gergely Nagy, Eva Varallyay, Matthew N. Poy, Judith E. Allen, Zsolt Bacso, Cei Abreu-Goodger, Laszlo Nagy
Journal: Genome Medicine (2016)

IL-4-driven alternative macrophage activation and proliferation are characteristic features of both antihelminthic immune responses and wound healing in contrast to classical macrophage activation, which primarily occurs during inflammatory responses. The signaling pathways defining the genome-wide microRNA expression profile as well as the cellular functions controlled by microRNAs during alternative macrophage activation are largely unknown. Hence, in the current work we examined the regulation and function of IL-4-regulated microRNAs in human and mouse alternative macrophage activation. We utilized microarray-based microRNA profiling to detect the dynamic expression changes during human monocyte–macrophage differentiation and IL-4-mediated alternative macrophage activation. The expression changes and upstream regulatory pathways of selected microRNAs were further investigated in human and mouse in vitro and in vivo models of alternative macrophage activation by integrating small RNA-seq, ChIP-seq, ChIP-quantitative PCR, and gene expression data. MicroRNA-controlled gene networks and corresponding functions were identified using a combination of transcriptomic, bioinformatic, and functional approaches. The IL-4-controlled microRNA expression pattern was identified in models of human and mouse alternative macrophage activation. IL-4-dependent induction of miR-342-3p and repression of miR-99b along with miR-125a-5p occurred in both human and murine macrophages in vitro. In addition, a similar expression pattern was observed in peritoneal macrophages of Brugia malayi nematode-implanted mice in vivo. By using IL4Rα- and STAT6-deficient macrophages, we were able to show that IL-4-dependent regulation of miR-342-3p, miR-99b, and miR-125a-5p is mediated by the IL-4Rα–STAT6 signaling pathway. The combination of gene expression studies and chromatin immunoprecipitation experiments demonstrated that both miR-342-3p and its host gene, EVL, are coregulated directly by STAT6. Finally, we found that miR-342-3p is capable of controlling macrophage survival through targeting an anti-apoptotic gene network including Bcl2l1. Our findings identify a conserved IL-4/STAT6-regulated microRNA signature in alternatively activated human and mouse macrophages. Moreover, our study indicates that miR-342-3p likely plays a pro-apoptotic role in such cells, thereby providing a negative feedback arm to IL-4-dependent macrophage proliferation.
On clinical trial participation.
Authors: B Fisher
Journal: Journal of Clinical Oncology (1991)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1991.9.11.1927 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 1941050 On clinical trial participation. B FisherxB FisherSearch for articles by this author https://doi.org/10.1200/JCO.1991.9.11.1927 First Page PDF © 1991 by American Society of Clinical Oncology
PTH-033 An ogd too many: investigation of iron deficiency anaemia
Authors: S Kotha, K McLaren, A Gera, A Loganayagam
Journal: Gut (2015)

<h3>Introduction</h3> Iron deficiency anaemia (IDA) occurs in 2–5% of adult men and postmenopausal women in the developed world. The most common cause of IDA in men and postmenopausal women is blood loss from the GI tract. The British Society of Gastroenterology recommends that “upper and lower GI investigations should be considered in all postmenopausal female and all male patients, where IDA has been confirmed unless there is a history of significant overt non-GI blood loss”. The main aim of this study was to determine if unnecessary oesophagogastroduodenoscopy (OGD) and duodenal biopsies were being performed in patients with the referral indication of iron deficiency anaemia. <h3>Method</h3> We reviewed retrospective data collected from ADAM (endoscopy database) at Queen Elizabeth Hospital for a period of 1 year (2013) for all the OGDs and duodenal biopsies undertaken, with the referral indication of IDA. We analysed all the haematology and biochemistry results for these patients from our laboratory system (Win path). The lowest haemoglobin (Hb) result from the 3 months prior to OGD and any haematinic results were recorded. The assessment of anaemia was based on our laboratory Hb ranges of 118–148 g/L for females and 133–167 g/L for males. Those with low mean corpuscular volume (MCV) but no haematinic results were assumed to have IDA in our analysis. Patients with signs of IDA on blood film were also included. <h3>Results</h3> 331 patients underwent an OGD during the study period for the referral indication of IDA. All 331 patients had duodenal biopsies taken. 31 patients (9.3%) were not anaemic.161 patients (48.6%) had no evidence of IDA.31 patients (9.3%) had positive findings on duodenal biopsy, but only 7(2%) patients needed active management based on histology (6 had histology consistent with coeliac disease and 1 was positive for giardia) and the other 24 patients had non-specific findings. There were no significant complications in any of our patients. <h3>Conclusion</h3> Clearly, a large number of patients (48.6%) who do not have evidence of IDA were undergoing an OGD. None of the patients had any complications from this invasive procedure. The procedure and analysis of duodenal biopsies is a great expense on the health care system (£700/OGD and £33.6/Biopsy). The introduction of a stringent screening system is needed for referrals with IDA to ensure that appropriate patients are undergoing invasive investigations. <h3>Disclosure of interest</h3> None Declared.
Similar Dynamics Of Intra Apheresis Autologous CD34+ Recruitment and Collection Efficiency In Patients Undergoing Mobilization With Or Without Plerixafor
Authors: Henning Schade, Yubin Kang, Chhabra Saurabh, Robert K Stuart, Kathy H Edwards, Cindy Kramer, Mollie Schneider, Amanda Littleton, Katie B Shoptaw, Luciano J Costa
Journal: Blood (2013)
Variations in care quality occur across the whole week, not just at weekends
Authors: Kevin Stewart, Ben Bray, Rhona Buckingham, Chris Boulton
Journal: BMJ (2016)

The “weekend effect” is an oversimplification.1 Attempting to address it is a distraction because hospital mortality is not a good measure of quality of care and weekends are not the only times when quality is compromised by the way in which services are organised.

What we need to know is, firstly, are there variations in quality of care depending on the time of day or the day of the week that emergency patients are admitted? Secondly, are these variations clinically important? Thirdly, if they are important, what are the underlying causes and, fourthly, does the NHS want to make the changes and investment that are necessary to deal with the causes?

We think that we can answer the first and second questions, at least for some groups of patients, using data from national clinical audits. Patients with stroke receive high …
Genetic studies yield clues to the pathogenesis of Langerhans cell histiocytosis
Authors: Li Zhang, Joel Moss
Journal: European Respiratory Journal (2016)

Interstitial lung diseases (ILDs) comprise a heterogeneous group of rare respiratory disorders characterised by diffuse pulmonary infiltrates and destruction of lung parenchyma [1]. With growing evidence that mutations in genes encoding proteins that participate in critical regulatory pathways have roles in the pathogenesis of some forms of ILD, it appears that some diseases under the ILD umbrella may be neoplastic and associated with the presence of cancer-like cells, not found in healthy individuals [2]. For example, lymphangioleiomyomatosis (LAM) results from the proliferation of LAM cells with mutation of tuberous sclerosis ( TSC ) 1 and TSC2 genes. LAM can be sporadic or occur in association with TSC, an autosomal dominant disorder [3]. TSC2 mutations were detected in seven (50%) out of 14 and a TSC1 mutation in one (7.1%) out of 14 TSC-LAM patients [4]. Sporadic LAM appears to be driven by TSC2 mutation [5]. The proteins encoded by TSC1 and TSC2 are upstream of the mammalian target of rapamycin pathway, which has been targeted in LAM treatment (Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus (MILES) trial) [6]. Identifying new therapeutic targets of interstitial lung disease from genetic studies <http://ow.ly/ZTv9U>
Avoiding treatment errors: a suggestion.
Authors: J Richard
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.11.2860 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7595750 Avoiding treatment errors: a suggestion. J RichardxJ RichardSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.11.2860 PDF "Avoiding treatment errors: a suggestion.." Journal of Clinical Oncology, 13(11), p. 2860© 1995 by American Society of Clinical Oncology
Acne
Authors: Janet M. Torpy
Journal: JAMA (2004)

Acne Hair follicles (the tiny pouches from which hairs grow) can become inflamed, especially on the face, chest, and back.This inflammation is called acne.Acne affects many individuals, especially in the teen years, but can last well into adulthood.Acne forms when the hair follicle produces excess oil, when the follicles are irritated (often from extra dead skin cells within the follicle), and when plugging of the pore (opening of the follicle) leads to increased bacteria in the follicle.Many treatments are available for acne and some may be used together.Dermatologists (doctors with specialized training in disorders of the skin) may offer advanced treatments to persons who have severe forms of acne or who have developed scars from their acne.The August 11, 2004, issue of JAMA includes an article about treatment of acne.
Absence of Detectable Deletions in the Mitochondrial Genome of Human Colon Tumors
Authors: B G Heerdt, L H Augenlicht
Journal: Cancer Communications (1990)

Changes in structure, function, and gene expression of mitochondria have been demonstrated in colorectal tumors (Wong, J.R.; Chen, L.B. Adv. Cell Biol. 2:263-290; 1988). In this report, mitochondrial DNA from 30 primary human colorectal tumors was compared to that of adjacent histologically normal colonic mucosa and human placenta. No evidence for substantial deletions in the major or minor population of mitochondrial DNA was detected, despite the fact that there are extensive deletions throughout the nuclear genome of such tumors. Hence, alterations in mitochondria in colorectal tumors must be dependent upon other mechanisms.
SAT0197 Biological Therapy and Radiosynoviorthesis in Patients with Rheumatoid Arthritis
Authors: M. Szentesi, Z. Nagy, P. Geher
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The treatment of patients with rheumatoid arthritis (RA) has been spectaculary changed since the 19509s. Introduction of the steroid compounds and their local application, the chemical and radionuclide synovectomy, surgical synovectomy, use of non steroid drugs, the basic treatment and the spread of biological therapy are the most important steps. Introduction of the biological therapy has changed the quality of life for these patients. <h3>Objectives</h3> During biological therapy sometimes 1 or 2 joints could be affected by inflammation. In this cases always the question is how to solve the problem. Change of the biological or basic therapy, use surgical synovectomy or radiosynovectomy (RSO)? <h3>Methods</h3> In our reumatological department 1500 patients with RA were treated with biological therapy between 2002 and 2014. In 100 patients we applied RSO because of the inflammation of the knee joint during biological therapy. We made a long term follow-up in 62 patient. All participants provided written informed consent. In all participants inflammatory knee joint disease was diagnosed on the basis of the American College of Rheumatology. 55 of 62 patients with rheumatoid arthritis were seropositive, 7 seronegative. Mean age of 8 male and 56 female patients was 51.4 years (range 24-79) years. In 32 patients the right knee, in 30 the left knee was treated by radiosynovectomy. Steinbrocker functional stadium II was observed in 52, stadium III in 10. Mean duration of disease was 7.3 years (range 0.5-25), of synovitis (6.3month (range 3-8) Mean number of punctions of the treated joint prior to radiosynovectomy was 4,2 per patient and of steroid administrations prior to radiosynovectomy 3,0. In 12 patients a systemic steroid therapy has been performed. <h3>Results</h3> During the study period, inflammation decreased. In the first two years excellent and good results were recorded in 82,2%. Two years after radiosynoviorthesis 83.3% of patients did not need another punction. Before the knee inflammation patients were in complete remission which status has been achieved after RSO as well. DAS: 2,4±0,4. <h3>Conclusions</h3> RSO is an effective method to treat the inflammation of the knes. The RSO performed during biological tehrapy is as effective as in the case of patients without biological therapy. In case of a succesful RSO there is no need for biological or basic therapy neither for surgical synovectomy. However an intraarticular injection has a low risk for infection it is recomended to avoid the biological therapy during the RSO. <h3>Disclosure of Interest</h3> None declared
AB0227 Anti Citrullinated Protein Antibody (ACPA) in Relation to Serum Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) and Disease Activity in Rheumatoid Arthritis
Authors: A.F. Elbelasy, H. Korayem, I. Khalil, M. Elsawy
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Bone destruction in rheumatoid arthritis (RA) remains a main concern in the clinical practice where the destructed joints may lead to impaired normal functional activity of patients. Antibodies against citrullinated proteins (ACPA) and high levels of Receptor activator of nuclear factor kappa-B ligand (RANKL) have been linked to altered bone metabolism in RA including more osteoclastic activity predicting more severe course of RA and more joints erosion. <h3>Objectives</h3> To investigate ACPA in RA patients in relation to serum RANKL and disease activity in Rheumatoid arthritis. <h3>Methods</h3> Sera of 40 patients diagnosed as RA according to EULAR/ACR 2010 divided into two equal groups of 20 ACPA positive and 20 ACPA negative patient9s group where RANKL was measured by enzyme linked immunosorbant assays (ELISA) and Results were correlated with disease activity using DAS28-CRP score. <h3>Results</h3> RANKL concentration was significantly higher in ACPA positive RA patients as compared to ACPA negative RA patients and Higher RANKL concentration was associated with higher disease activity measured using the DAS-CRP 28. <h3>Conclusions</h3> ACPA positive RA patients are associated with increased levels of RANKL and high disease activity in relation to ACPA negative patients. <h3>References</h3> Hensvold, Aase Haj, Joshua, Vijay, Saevarsdottir, Saedis, Larkin, Michaela, Israelsson, Lena, Qureshi, Ferhan, et al; Autoantibodies To Citrullinated Proteins Associate With Bone Destruction Marker and Are Modulated By First Anti Rheumatic Treatment In Early Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2013;65 Suppl 10:1327 DOI: 10.1002/art.2013.65.issue-s10. Syversen SW, Gaarder PI, Goll GL, Ødegård S, Haavardsholm EA, Mowinckel P, et al. High anti-CCP levels and an algorithm of four variables predict radiographic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study. Ann Rheum Dis 2007. Aletaha D, Neogi T, Silman AJ, et al. Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2010;69:1580-8. Geusens, P. P., Landewé, R. B. M., Garnero, P., et al. The ratio of circulating osteoprotegerin to RANKL in early rheumatoid arthritis predicts later joint destruction. Arthritis &amp; Rheumatism, 54: 1772–1777. doi: 10.1002/art.21896. <h3>Acknowledgements</h3> I would like to thank my professors supervising my research for their support during every step working through this research and my father prof of rheumatology for his support in the medical field and his encouargment. <h3>Disclosure of Interest</h3> None declared
Effect of atrasentan (ABT-627, ATN) on the pharmacokinetics (PK) of fexofenadine (FEX)
Authors: C. E. Klein, M. C. Schroeder, I. Facey, Q. Wang, D. Grimm, T. Yanke, E. Everitt, R. A. Carr, T. Doan, A. Allen
Journal: Journal of Clinical Oncology (2004)

4723 Background: ATN is an oral selective endothelin A receptor antagonist in phase 3 clinical development for treatment of hormone-refractory prostate cancer. ATN is not a p-glycoprotein (Pgp) substrate, but inhibits Pgp with an IC50 ∼12 μM (>50-fold the mean plasma Cmax for 10 mg/d ATN, although maximal intestinal concentrations may be 80 μM). The antihistamine FEX is a sensitive probe Pgp substrate; in clinical trials, Pgp inhibitors erythromycin and ketoconazole increased FEX AUC >2-fold. Methods: To assess the effect of ATN on FEX PK, a phase 1 open label study was conducted in 12 healthy subjects (10 M and 2 F; mean±SD 27±9 yrs, 75±10 kg). Subjects received FEX 120 mg PO on Days 1 and 8, and ATN 10 mg PO QD from Day 3 through 9. Blood and urine samples for FEX assay were collected predose and over 48 h after each FEX dose. Plasma and urine concentrations of FEX were determined using validated LC/MS/MS methods. Results: FEX PK are summarized (mean±SD; N=11) in the following table. We observed no meaningful effect of MDR-1 genotype on FEX PK, nor on changes of FEX PK following dosing with ATN. FEX with ATN was generally well tolerated. One subject did not receive ATN on Days 7–8 and was excluded from PK analyses. Most AEs were mild; headache was the most common AE. Conclusions: ATN increased FEX bioavailability but did not alter FEX elimination, indicating that 10 mg QD ATN does not affect systemic Pgp activity. Pgp inhibition in the gut appears to be a local effect of orally administered ATN and therefore PK interactions would only be expected between ATN and absorption-limited Pgp substrates. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories
Clinical correlates of platelet prostaglandin receptor subsensitivity in schizophrenia
Authors: P D Kanof, M Davidson, C A Johns, R C Mohs, K L Davis
Journal: American Journal of Psychiatry (1987)

A diminished cAMP response to prostaglandin E1 (PGE1) in platelets from schizophrenic patients has been demonstrated previously. The authors report that among 35 actively psychotic male schizophrenic patients, the platelet cAMP response to PGE1 was negatively correlated with global symptom severity and with several indexes of positive symptom severity but not with negative symptom severity. If this subsensitivity of platelet PGE receptors extends to brain PGE receptors, schizophrenic patients may have an impairment in the ability of endogenous PGEs to inhibit dopaminergic transmission. Such impairment could have a permissive effect on the production of psychotic symptoms during exacerbations in schizophrenic patients.
Unintended Consequences
Authors: Artaza Gilani
Journal: JAMA (2013)

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Submicroscopic Particles in Normal Bovine and Human Milks: A Preliminary Morphological Survey&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E. M. Jensen, G. Schidlovsky
Journal: JNCI Journal of the National Cancer Institute (1964)

This paper describes 5 general types of particles, observed by electron microscopy, in II negatively stained or sectioned samples of normal pasteurized cow's milk and 2 of raw pooled milk. Particles were also seen in 2 samples of presumably normal human milk. The evidence for or against the viral nature of these particles is discussed. The morphology of certain particles is compared to the murine leukemia virus particles. Some features resembling influenza and mouse mammary tumor particles are noted. Structures resembling pleuropneumonia-like organisms are also described. None of the particles were positively identified as viruses.
Multistage Models for Carcinogenesis
Authors: Suresh Moolgavkar, M.D.
Journal: JNCI Journal of the National Cancer Institute (1980)

Multistage Models for Carcinogenesis Get access Suresh Moolgavkar, M.D. Suresh Moolgavkar, M.D. The Institute for Cancer Research 7701 Burholme Avenue, Fox Chase, Philadelphia, Pennsylvania 19111 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 65, Issue 2, August 1980, Page 215, https://doi.org/10.1093/jnci/65.2.215 Published: 01 August 1980