tbuckley/cabot-search huggingface dataset:
Nucleosome accumulation and reduction of C-reactive protein are associated with the generation of anti-nuclear antibodies in patients with rheumatoid arthritis treated with adalimumab, but not with etanercept
Authors: R Priori, C Alessandri, L Magrini, E A M Cassarà, F Ceccarelli, M Modesti, C Croia, M Bombardieri, G Valesini
Journal: Annals of the Rheumatic Diseases (2009)

During the last decade, three tumour necrosis factor (TNF)α antagonists have been approved for the treatment of moderate to severe rheumatoid arthritis (RA).1 These new drugs, while extremely powerful, can induce puzzling biological phenomena such as the production of autoantibodies whose extent seems to vary accordingly to the drug used.2,3

A dysregulation of apoptosis with exposition of nuclear antigens and consequent rapid (within hours) accumulation of nucleosomes has been evoked to explain autoantibody occurrence in patients treated with infliximab.4 In addition (or in alternative) to an increased release of nuclear antigens, a defect in clearance mechanisms can play a role in the generation of autoantibodies.5

We studied autoantibody profiles (anti-nuclear antibody (ANA), anti-double stranded …
Functional Somatic Syndromes
Authors: Terry E. Hedrick
Journal: Annals of Internal Medicine (2000)

Letters15 February 2000Functional Somatic SyndromesTerry E. Hedrick, PhDTerry E. Hedrick, PhDCobb Island, MD 20625 (Hedrick)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-4-200002150-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:While reading Barsky and Borus's article (1), I felt that I had stepped back into the Dark Ages. Not only did this article label a surprisingly diverse set of illnesses as “functional somatic,” but it managed to omit hundreds of peer-reviewed articles documenting physiologic bases for illnesses such as the chronic fatigue syndrome. Where are the references to the research on neurally mediated hypotension being done at Johns Hopkins, investigation into defects in the viral defense system being done at Temple University, and work done at the National Institutes of Health-funded chronic fatigue syndrome center run by ...References1. Barsky AJ, Borus JF. Functional somatic syndromes. Ann Intern Med. 1999;130:910-21. LinkGoogle Scholar2. Natelson B. Facing and Fighting Fatigue: A Practical Approach. New Haven: Yale Univ Pr; 1998. Google Scholar3. Jason LA, Richman JA, Friedberg F, Wagner L, Taylor R, Jordan KM. Politics, science and the emergence of a new disease. American Psychologist. 1997;52:973-83. CrossrefMedlineGoogle Scholar4. Deale A, Chalder T, Wesseley S. Illness beliefs and treatment outcome in chronic fatigue syndrome. Psychosom Res. 1998;45:77-83. CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Terry E. Hedrick, PhDAffiliations: Cobb Island, MD 20625 (Hedrick) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoFunctional Somatic Syndromes Arthur J. Barsky and Jonathan F. Borus Functional Somatic Syndromes James McSherry Functional Somatic Syndromes Kenneth Clemenger Functional Somatic Syndromes Allan Clemenger Functional Somatic Syndromes Ellen Goudsmit Functional Somatic Syndromes Melody Heard Functional Somatic Syndromes Frank Albrecht Functional Somatic Syndromes Thomas L. English Functional Somatic Syndromes Thomas L. Kurt Functional Somatic Syndromes Arthur J. Barsky and Jonathan F. Borus Metrics Cited byCentral Sensitivity Syndromes: A New Paradigm and Group Nosology for Fibromyalgia and Overlapping Conditions, and the Related Issue of Disease versus IllnessMedically unexplained physical symptoms in medical practice: a psychiatric perspective. 15 February 2000Volume 132, Issue 4 Page: 327 Keywords Chronic fatigue syndrome Emotions Hypotension ePublished: 15 August 2000 Issue Published: 15 February 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts
Authors: Sonia Vallet, Noopur Raje, Kenji Ishitsuka, Teru Hideshima, Klaus Podar, Shweta Chhetri, Samantha Pozzi, Iris Breitkreutz, Tanyel Kiziltepe, Hiroshi Yasui, Enrique M. Ocio, Norihiko Shiraishi, Janice Jin, Yutaka Okawa, Hiroshi Ikeda, Siddhartha Mukherjee, Nileshwari Vaghela, Diana Cirstea, Marco Ladetto, Mario Boccadoro, Kenneth C. Anderson
Journal: Blood (2007)

The interaction between osteoclasts (OCs) and multiple myeloma (MM) cells plays a key role in the pathogenesis of MM-related osteolytic bone disease (OBD). MM cells promote OC formation and, in turn, OCs enhance MM cell proliferation. Chemokines are mediators of MM effects on bone and vice versa; in particular, CCL3 enhances OC formation and promotes MM cell migration and survival. Here, we characterize the effects of MLN3897, a novel specific antagonist of the chemokine receptor CCR1, on both OC formation and OC-MM cell interactions. MLN3897 demonstrates significant impairment of OC formation (by 40%) and function (by 70%), associated with decreased precursor cell multinucleation and down-regulation of c-fos signaling. OCs secrete high levels of CCL3, which triggers MM cell migration; conversely, MLN3897 abrogates its effects by inhibiting Akt signaling. Moreover, MM cell-to-OC adhesion was abrogated by MLN3897, thereby inhibiting MM cell survival and proliferation. Our results therefore show novel biologic sequelae of CCL3 and its inhibition in both osteoclastogenesis and MM cell growth, providing the preclinical rationale for clinical trials of MLN3897 to treat OBD in MM.
Ionising radiation in infancy and adult cognitive function
Authors: Per Hall, Marie Lundell
Journal: BMJ (2004)

Editor—We agree with Meara et al that optimising computed tomography protocols is crucial.

Fogelholm raises the possibility of the study subjects having Sturge-Weber syndrome—cutaneous and cerebral haemangiomas linked to neurological symptoms such as epileptic seizures and mental retardation. We matched the cohort with the Swedish inpatient registry and compared the observed and expected number of admissions for epilepsy. In all, 19 boys had been admitted under this diagnosis, which was non-significantly fewer than expected. Sturge-Weber syndrome is not likely to have influenced our findings.

Ehrle says that we have ignored a large body of evidence and says that little is known about the effects of low doses of radiation or a possible threshold value. One of the most important studies in this field estimated cancer risks in 50 000 survivors of the atomic bomb, focusing on those having been exposed to < 500 mSv.1 A linear no threshold model fitted the data, but they could not exclude a possible threshold of 60 mSv.

Prabhu points out that x ray treatments during 1930-60 had less penetration than today. However, in our study only 6% received x ray treatment and the remaining patients were treated with radium-226 applicators. The envelopes of the applicators absorbed α and β rays and the main dose contribution to the brain came from the γ rays.

Prabhu also asserts that, at least in the United Kingdom, careful discussion takes place before deciding on computed tomography for young children and that only necessary examinations are conducted. Let's just hope that he is correct, that his colleagues follow his example, and that this behaviour quickly spreads outside the United Kingdom.
Medical courts could ease US malpractice crisis, group says
Authors: Jeanne Lenzer
Journal: BMJ (2005)

Researchers at the Harvard School of Public Health and the charity Common Good, which is based in Washington, DC, and campaigns for legal reform, have been awarded grants totalling almost $1.5m (£0.8m; €1.2m) by the Robert Wood Johnson Foundation to design a medical court system that would replace jurors with expert panellists.

The move stems from the malpractice litigation crisis in the United States, which has led to controversy as some doctors have closed their practices, leaving areas of the country without obstetricians, orthopaedists, or neurosurgeons. It has also led a coalition of medical and health policy experts and the US Senate majority leader, Dr Bill Frist, to propose the creation of medical courts. …
92 FORCED IL-6 SIGNALING IS SUFFICIENT TO PROMOTE MALIGNANT TRANSFORMATION IN TELOMERASE-IMMORTALIZED HUMAN FETAL HEPATOCYTES FOLLOWING CHALLENGE WITH OXIDATIVE STRESS
Authors: D. Heim, A.C. Parplys, S. Rose-John, A.W. Lohse, E. Dikomey, H. Wege
Journal: Journal of Hepatology (2013)
Asbestos Exposure—Cigarette Smoking Interactions Among Shipyard Workers
Authors: Paul D. Blanc
Journal: JAMA (1988)

We studied the roentgenograms, pulmonary function tests, and physical findings of 294 shipyard workers to evaluate asbestos exposure-cigarette smoking interactions. Roentgenographic parenchymal opacities, decreased pulmonary diffusing capacity for carbon monoxide, decreased flow at low lung volume, rales, and clubbing were each significantly related to the number of years elapsed since first exposure to asbestos and cigarette smoking status when analyzed by logistic regression. A dose-dependent cigarette smoking response that was consistent with synergism was present only for parenchymal opacities and decreased flow at low lung volume. These findings suggest that decreased flow at low lung volume, possibly reflecting peribronchiolar fibrosis, may be a functional corollary to smoking-associated parenchymal roentgenographic opacities among some asbestos-exposed individuals.
Erythrocyte glutamine depletion, altered redox environment, and pulmonary hypertension in sickle cell disease
Authors: Claudia R. Morris, Jung H. Suh, Ward Hagar, Sandra Larkin, D. Anton Bland, Martin H. Steinberg, Elliott P. Vichinsky, Mark Shigenaga, Bruce Ames, Frans A. Kuypers, Elizabeth S. Klings
Journal: Blood (2007)
Carrier Testing for Severe Childhood Recessive Diseases by Next-Generation Sequencing
Authors: Callum J. Bell, Darrell L. Dinwiddie, Neil A. Miller, Shannon L. Hateley, Elena E. Ganusova, Joann Mudge, Ray J. Langley, Lu Zhang, Clarence C. Lee, Faye D. Schilkey, Vrunda Sheth, Jimmy E. Woodward, Heather E. Peckham, Gary P. Schroth, Ryan W. Kim, Stephen F. Kingsmore
Journal: Science Translational Medicine (2011)

Carrier testing for 448 severe childhood recessive diseases by next-generation sequencing has good predictive value and suggests that every individual carries about three disease mutations.
Expression of insulin like growth factor (IGF-II) and of the IGF II receptor (IGF-IIR) in normal and cirrhotic human liver
Authors: N. Sedlacek, H. Herbst, A. Hasilik, P. Neuhaus, W.O. Bechstein, E.O. Riecken, D. Schuppan
Journal: Journal of Hepatology (1998)
Benefits and Risks of Anticoagulation Resumption Following Traumatic Brain Injury
Authors: Jennifer S. Albrecht, Xinggang Liu, Mona Baumgarten, Patricia Langenberg, Gail B. Rattinger, Gordon S. Smith, Steven R. Gambert, Stephen S. Gottlieb, Ilene H. Zuckerman
Journal: JAMA Internal Medicine (2014)

<h3>Importance</h3> The increased risk of hemorrhage associated with anticoagulant therapy following traumatic brain injury creates a serious dilemma for medical management of older patients: Should anticoagulant therapy be resumed after traumatic brain injury, and if so, when? <h3>Objective</h3> To estimate the risk of thrombotic and hemorrhagic events associated with warfarin therapy resumption following traumatic brain injury. <h3>Design, Setting, and Participants</h3> Retrospective analysis of administrative claims data for Medicare beneficiaries aged at least 65 years hospitalized for traumatic brain injury during 2006 through 2009 who received warfarin in the month prior to injury (n = 10 782). <h3>Intervention</h3> Warfarin use in each 30-day period following discharge after hospitalization for traumatic brain injury. <h3>Main Outcomes and Measures</h3> The primary outcomes were hemorrhagic and thrombotic events following discharge after hospitalization for traumatic brain injury. Hemorrhagic events were defined on inpatient claims using<i>International Classification of Diseases, Ninth Revision, Clinical Modification</i>codes and included hemorrhagic stroke, upper gastrointestinal bleeding, adrenal hemorrhage, and other hemorrhage. Thrombotic events included ischemic stroke, pulmonary embolism, deep venous thrombosis, and myocardial infarction. A composite of hemorrhagic or ischemic stroke was a secondary outcome. <h3>Results</h3> Medicare beneficiaries with traumatic brain injury were predominantly female (64%) and white (92%), with a mean (SD) age of 81.3 (7.3) years, and 82% had atrial fibrillation. Over the 12 months following hospital discharge, 55% received warfarin during 1 or more 30-day periods. We examined the lagged effect of warfarin use on outcomes in the following period. Warfarin use in the prior period was associated with decreased risk of thrombotic events (relative risk [RR], 0.77 [95% CI, 0.67-0.88]) and increased risk of hemorrhagic events (RR, 1.51 [95% CI, 1.29-1.78]). Warfarin use in the prior period was associated with decreased risk of hemorrhagic or ischemic stroke (RR, 0.83 [95% CI, 0.72-0.96]). <h3>Conclusions and Relevance</h3> Results from this study suggest that despite increased risk of hemorrhage, there is a net benefit for most patients receiving anticoagulation therapy, in terms of a reduction in risk of stroke, from warfarin therapy resumption following discharge after hospitalization for traumatic brain injury.
African refugee disasters increase the risk of blindness
Authors: D. Heiden
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Reports of the crisis in Rwanda make it plain that African refugee disasters are accompanied by excessive mortality.<sup>1</sup>We present evidence that risk of blindness is dramatically increased as well. In 1987, 2 years after the Ethiopian famine, we performed eye studies in the refugee camps of the eastern Sudan. In addition to random cluster surveys for blindness, we directed particular attention to corneal scars, as a proxy for the uncommon event of blindness. If a person had a corneal scar, it was reasonable to assume that the person had sustained a potentially blinding illness, such as serious eye infection, xerophthalmia, or trauma. We were interested to see if there was evidence that the catastrophic shearing of the social fabric caused by the refugee disaster could be related to the prevalence or incidence of corneal scar. We compared children orphaned by the refugee crisis with children
Histone H3 lysine 9 di-methylation as an epigenetic signature of the interferon response
Authors: Terry C. Fang, Uwe Schaefer, Ingrid Mecklenbrauker, Astrid Stienen, Scott Dewell, Marie S. Chen, Inmaculada Rioja, Valentino Parravicini, Rab K. Prinjha, Rohit Chandwani, Margaret R. MacDonald, Kevin Lee, Charles M. Rice, Alexander Tarakhovsky
Journal: The Journal of Experimental Medicine (2012)

Effective antiviral immunity depends on the ability of infected cells or cells triggered with virus-derived nucleic acids to produce type I interferon (IFN), which activates transcription of numerous antiviral genes. However, disproportionately strong or chronic IFN expression is a common cause of inflammatory and autoimmune diseases. We describe an epigenetic mechanism that determines cell type–specific differences in IFN and IFN-stimulated gene (ISG) expression in response to exogenous signals. We identify di-methylation of histone H3 at lysine 9 (H3K9me2) as a suppressor of IFN and IFN-inducible antiviral gene expression. We show that levels of H3K9me2 at IFN and ISG correlate inversely with the scope and amplitude of IFN and ISG expression in fibroblasts and dendritic cells. Accordingly, genetic ablation or pharmacological inactivation of lysine methyltransferase G9a, which is essential for the generation of H3K9me2, resulted in phenotypic conversion of fibroblasts into highly potent IFN-producing cells and rendered these cells resistant to pathogenic RNA viruses. In summary, our studies implicate H3K9me2 and enzymes controlling its abundance as key regulators of innate antiviral immunity.
Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer.
Authors: M A Sovak, R E Bellas, D W Kim, G J Zanieski, A E Rogers, A M Traish, G E Sonenshein
Journal: Journal of Clinical Investigation (1997)

Expression of nuclear factor-kappaB (NF-kappaB)/Rel transcription factors has recently been found to promote cell survival, inhibiting the induction of apoptosis. In most cells other than B lymphocytes, NF-kappaB/Rel is inactive, sequestered in the cytoplasm. For example, nuclear extracts from two human untransformed breast epithelial cell lines expressed only very low levels of NF-kappaB. Unexpectedly, nuclear extracts from two human breast tumor cell lines displayed significant levels of NF-kappaB/Rel. Direct inhibition of this NF-kappaB/ Rel activity in breast cancer cells induced apoptosis. High levels of NF-kappaB/Rel binding were also observed in carcinogen-induced primary rat mammary tumors, whereas only expectedly low levels were seen in normal rat mammary glands. Furthermore, multiple human breast cancer specimens contained significant levels of nuclear NF-kappaB/Rel subunits. Thus, aberrant nuclear expression of NF-kappaB/Rel is associated with breast cancer. Given the role of NF-kappaB/Rel factors in cell survival, this aberrant activity may play a role in tumor progression, and represents a possible therapeutic target in the treatment of these tumors.
Effects of the putative neutrophil-generated toxin, hypochlorous acid, on membrane permeability and transport systems of Escherichia coli.
Authors: J M Albrich, J H Gilbaugh, K B Callahan, J K Hurst
Journal: Journal of Clinical Investigation (1986)

Titrimetric addition of hypochlorous acid (HOCl) or chloramine (NH2Cl) to suspensions of Escherichia coli decreases their ability to accumulate 14C-labeled glutamine, proline, thiomethylgalactoside, and leucine in a manner that approximately coincides with loss of cell viability; quantitative differences in cellular response are observed with the two oxidants. Inhibition of beta-galactosidase activity in E. coli ML-35, a strain lacking functional lactose permease, is complex and also depends upon the identity of the oxidant. Membrane proton conductivities and glycerol permeabilities are unchanged by addition of HOCl or NH2Cl in excess of that required for inactivation. The combined results are interpreted to indicate that the locus of HOCl attack is the cell envelope, that HOCl inactivation does not occur by loss of membrane structural integrity, that loss of transport function can be identified with either selective oxidative inhibition of the transport proteins or loss of cellular metabolic energy, and that different mechanisms of inactivation may exist for HOCl and NH2Cl.
Hematopoietic recovery after IEV chemotherapy for malignant lymphoma followed by different cytokines can be monitored by analysis of Gα 16 and CD34
Authors: M. Pfeilstöcker, H. Karlic, J. Salamon, H. Mühlberger, B. Pavlova, H. Strobl, E. Pittermann, R. Heinz
Journal: American Journal of Hematology (2000)

The hematopoiesis-specific G protein α subunit Gα16 is a specific element in the signal transduction of the early hematopoietic cytokine network. As Gα16 mRNA can be detected in early hematopoietic progenitor cells, RT-PCR for Gα16 can be used as a sensitive marker of hematopoietic activity. The aim of this study was to test the possible use of Gα16 determinations for monitoring cytokine effects on hematopoietic recovery after chemotherapy in patients. We correlated presence of Gα16 mRNA and CD34 surface antigen with hematopoietic recovery in six lymphoma patients undergoing salvage therapy with different cytokine support (IEV followed by G-CSF, IL-3, or placebo). Regardless of different cytokine schedules with different time courses, hematopoietic recovery was always preceded by transcription of Gα16. Monitoring the expression of Gα16 mRNA by RT-PCR is a highly sensitive diagnostic tool for analyzing hematopoietic recovery after chemotherapy and for characterizing the effects of cytokines on hematopoiesis. Am. J. Hematol. 64:156–160, 2000. © 2000 Wiley-Liss, Inc.
Recovery of Femoral Head Perfusion after Drainage of Septic Joint
Authors: JOAN M. MACK, JOHN J. SZIKLAS, RONALD J. ROSENBERG, RICHARD P. SPENCER
Journal: Clinical Nuclear Medicine (1987)

A 64-year-old woman was febrile and had pain near the right hip. Blood cultures grew beta hemolytic streptococci. A bone scan showed reduced activity in the right femoral head and neck compared with the left femoral head and neck. She was treated with intravenous antibiotics and surgical decompression of a tense and bulging right hip joint. Five days later, a repeat bone scan revealed much of the femoral head activity to have returned. By day 20 after the initial bone image, there was intense activity throughout the femoral head and neck. Prompt relief of a distended hip joint can result in reperfusion of the femoral head and neck.
Elevated serum levels of 90K/MAC-2 BP predict unresponsiveness to α-interferon therapy in chronic HCV hepatitis patients
Authors: Marco Artini, Clara Natoli, Nicola Tinari, Antonio Costanzo, Rossana Marinelli, Clara Balsano, Patrizia Porcari, Domenico Angelucci, Maurizia D'Egidio, Massimo Levrero, Stefano Iacobelli
Journal: Journal of Hepatology (1996)