tbuckley/cabot-search huggingface dataset:
A1.1 Identification and phenotyping of innate lymphoid cells present in the diseased joints of patients with spondyloarthritis, rheumatoid arthritis and psoriatic arthritis
Authors: MH Al-Mossawi, J De Wit, B Kendrick, R Gundle, P Bowness
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and aims</h3> Innate lymphoid cells (ILCs) have been recently identified at a number of different tissues and are thought to be an important class of innate immune cells involved in the initiation of the inflammatory response during health and disease. It is not known whether these cells exist in the human joint. We set out to identify and characterise these cells in the joints of patients with inflammatory arthritis. <h3>Methods</h3> Matched synovial fluid and peripheral blood mononuclear cells from patients with spondyloarthritis (SpA) and psoriatic arthritis (PsA) were isolated and phenotyped using flow cytometry. In addition, cells from explanted orthopaedic surgical tissue samples were obtained from patients with SpA, PsA and rheumatoid arthritis (RA) and cultured in media containing interleukin-2 and interleukin-7. Intracellular cytokine staining was performed and analysed by flow cytometry. <h3>Results</h3> A population of lineage-negative (i.e. negative for CD3, CD5 CD8, CD11b, CD11c, CD14, CD19, CD20, CD34, TCR-γδ) CD45 positive, IL-7R positive cells was identified in the synovial fluid and tissue of diseased human joints. Further phenotyping showed these to be either C-KIT positive ILC3 cells or C-KIT negative ILC1 cells. CRTH2 positive ILC2 cells were not detected. Comparison of matched blood and synovial fluid cells showed ILC3 populations were enriched in the joint and expressed HLA-DR. <h3>Discussion and conclusions</h3> ILC populations (type 1 and type 3) are pre present in the synovial fluid and synovial tissue of inflamed SpA, PsA and RA joints. These cells are capable of rapid cytokine release and are potentially highly inflammatory. They may also play a role in antigen presentation through HLA-DR expression. Understanding the role of ILCs in health and disease is important for deciphering the processes taking part in early SpA pathogenesis.
CD34+ Hematopoietic Stem Cells Exert Accessory Function in Lipopolysaccharide-induced T Cell Stimulation and CD80 Expression on Monocytes
Authors: Taila Mattern, Gundolf Girroleit, Hans-Dieter Flad, Ernst T. Rietschel, Artur J. Ulmer
Journal: The Journal of Experimental Medicine (1999)

CD34+ hematopoietic stem cells, which circulate in peripheral blood with very low frequency, exert essential accessory function during lipopolysaccharide (LPS)-induced human T lymphocyte activation, resulting in interferon γ production and proliferation. In contrast, stimulation of T cells by “conventional” recall antigens is not controlled by blood stem cells. These conclusions are based on the observation that depletion of CD34+ blood stem cells results in a loss of LPS-induced T cell stimulation as well as reduced expression of CD80 antigen on monocytes. The addition of CD34-enriched blood stem cells resulted in a recovery of reactivity of T cells and monocytes to LPS. Blood stem cells could be replaced by the hematopoietic stem cell line KG-1a. These findings may be of relevance for high risk patients treated with stem cells or stem cell recruiting compounds and for patients suffering from endotoxin-mediated diseases.
Competing with injuries: injuries prior to and during the 15th FINA World Championships 2013 (aquatics)
Authors: Margo Mountjoy, Astrid Junge, Sarah Benjamen, Kevin Boyd, Mohamed Diop, David Gerrard, Cees-Rein van den Hoogenband, Saul Marks, Enrique Martinez-Ruiz, Jim Miller, Kyriakos Nanousis, Farhad Moradi Shahpar, Jose Veloso, William van Mechelen, Evert Verhagen
Journal: British Journal of Sports Medicine (2014)

Background Injury and illness surveillance is the foundation for the development of prevention strategies. Objective To examine injuries among the aquatic disciplines in the 4 weeks prior to and during the 2013 FINA World Championships. Methods The study was comprised of two components: (1) a retrospective athlete survey recording injuries in the 4 weeks prior to the Championships and (2) a prospective recording of injuries and illnesses by the medical teams of the participating countries and the local host medical team. Results One-third of the 1116 responding athletes reported an injury/physical complaint in the 4 weeks prior to the Championships. Significantly more women (36.7%) than men (28.6%) reported injuries. Divers reported the highest rate of injury/physical complaints (55.7%). At the start of the Championships, 70% of injured respondents (n=258) were still symptomatic; however, full participation was expected by 76%. During the Championships, 186 new injuries were reported (8.3/100 registered athletes) with the highest injury incidence rate in water polo (15.3/100 registered athletes). The most common injured body part was the shoulder (21%). A total of 199 illnesses were reported during the Championships (9.0/100 registered athletes) with the most common diagnosis of illness being gastrointestinal infection. Environmental exposure (allergy, otitis and jellyfish stings) was responsible for 27% of all illnesses in open water swimming. Conclusions Injuries pose a significant health risk for elite aquatic athletes. A prospective study would improve understanding of out-of-competition injuries. Future injury and illness surveillance at FINA World Championships is required to direct and measure the impact of prevention strategies.
Evaluation and Clinical Implications of Aortic Valve Calcification Measured by Electron-Beam Computed Tomography
Authors: David Messika-Zeitoun, Marie-Christine Aubry, Delphine Detaint, Lawrence F. Bielak, Patricia A. Peyser, Patrick F. Sheedy, Stephen T. Turner, Jerome F. Breen, Christopher Scott, A. Jamil Tajik, Maurice Enriquez-Sarano
Journal: Circulation (2004)

Background— Electron-beam computed tomography (EBCT) is used to measure coronary calcification but not for aortic valve calcification (AVC). Its accuracy, association with aortic stenosis (AS) severity, and diagnostic and prognostic value with respect to AVC are unknown. Methods and Results— In 30 explanted aortic valves, the AVC score by EBCT (1125±1294 Agatston units [AU]) showed a strong linear correlation ( r =0.96, P &lt;0.0001) with valvular calcium weight (653±748 mg) by pathology that allowed estimation of calcium weight as AVC score/1.7, with a small standard error of the estimate (53 mg). In 100 consecutive clinical patients, we measured AVC by EBCT and AS severity by echocardiographic aortic valve area (AVA). The AVC score was 1316±1749 AU (range 0 to 7226 AU). Intraobserver and interobserver variabilities were excellent (4±4% and 4±10%, respectively). AVC and AVA were strongly associated ( r =0.79, P &lt;0.0001) but had a curvilinear relationship that suggested that AVC and AVA provide complementary information. AVC score ≥1100 AU provided 93% sensitivity and 82% specificity for diagnosis of severe AS (AVA &lt;1 cm 2 ), with a receiver operator characteristic curve area of 0.89. AVC assessment by echocardiography was often more severe than by EBCT ( P &lt;0.0001). During follow-up, 22 patients either died, developed heart failure, or required surgery. With adjustment for age, sex, symptoms, ejection fraction, and AVA, the AVC score was independently predictive of event-free survival (risk ratio 1.06 per 100-AU increment [1.02 to 1.10], P &lt;0.001), even after adjustment for echocardiographic calcifications. Conclusions— AVC is accurately and reproducibly measured by EBCT and shows a strong association and diagnostic value for severe AS. The curvilinear relationship between AVC and AVA suggests these measures are complementary, and indeed, AVC provides independent outcome information. Thus, AVC is an important measurement in the evaluation of patients with AS.
Effects of oleate-rich and linoleate-rich diets on the susceptibility of low density lipoprotein to oxidative modification in mildly hypercholesterolemic subjects.
Authors: P Reaven, S Parthasarathy, B J Grasse, E Miller, D Steinberg, J L Witztum
Journal: Journal of Clinical Investigation (1993)

We report the results of feeding oleate- or linoleate-enriched diets for 8 wk to mildly hypercholesterolemic subjects and the resulting alterations in composition and functional properties of their plasma LDL and HDL. LDL isolated from subjects on oleate-enriched diets was less susceptible to copper-mediated oxidation, as measured by conjugated diene and lipid peroxide formation, and less susceptible to LDL-protein modification, as evidenced by reduced LDL macrophage degradation after copper- or endothelial cell-induced oxidation. For all subjects, the percentage of 18:2 in LDL correlated strongly with the extent of conjugated diene formation (r = 0.89, P < 0.01) and macrophage degradation (r = 0.71, P < 0.01). Oxidation of LDL led to initial rapid depletion of unsaturated fatty acids in phospholipids followed by extensive loss of unsaturated fatty acids in cholesteryl esters and triglycerides. Changes in HDL fatty acid composition also occurred. However, HDL from both dietary groups retained its ability to inhibit oxidative modification of LDL. This study demonstrates that alterations in dietary fatty acid composition can effectively alter the fatty acid distribution of LDL and HDL in hypercholesterolemic subjects and that susceptibility to LDL oxidation is altered by these changes. Substitution of monounsaturated (rather than polyunsaturated) fatty acids for saturated fatty acids in the diet might be preferable for the prevention of atherosclerosis.
A Retrospective Analysis of Oxaliplatin, Irinotecan and PK-Adjusted 5-Fluorouracil Within a Neoadjuvant Multidisciplinary Approach in Locally Advanced Pancreatic Cancer (LAPC) Patients
Authors: Martin Romano Patricia, A. Aldaz, J.P. Fusco, J.J. Sola, A. Chopitea, J.C. Subtil, J. Solorzano, F. Pardo, L. Arbea, C. Garzon, F. Rotellar, L. Zufia, J. Rodriguez
Journal: Annals of Oncology (2014)
Genetic Influences on the End-Stage Effector Phase of Arthritis
Authors: Hong Ji, Dominique Gauguier, Koichiro Ohmura, Antonio Gonzalez, Veronique Duchatelle, Patrick Danoy, Henri-Jean Garchon, Claude Degott, Mark Lathrop, Christophe Benoist, Diane Mathis
Journal: The Journal of Experimental Medicine (2001)

K/B×N T cell receptor transgenic mice are a model of inflammatory arthritis, most similar to rheumatoid arthritis, that is critically dependent on both T and B lymphocytes. Transfer of serum, or just immunoglobulins, from arthritic K/B×N animals into healthy recipients provokes arthritis efficiently, rapidly, and with high penetrance. We have explored the genetic heterogeneity in the response to serum transfer, thereby focussing on the end-stage effector phase of arthritis, leap-frogging the initiating events. Inbred mouse strains showed clear variability in their responses. A few were entirely refractory to disease induction, and those which did develop disease exhibited a range of severities. F1 analyses suggested that in most cases susceptibility was controlled in a polygenic additive fashion. One responder/nonresponder pair (C57Bl/6 × NOD) was studied in detail via a genome scan of F2 mice; supplementary information was provided by the examination of knock-out and congenic strains. Two genomic regions that are major, additive determinants of the rapidity and severity of K/B×N serum-transferred arthritis were highlighted. Concerning the first region, on proximal chromosome (chr)2, candidate assignment to the complement gene C5 was confirmed by both strain segregation analysis and functional data. Concerning the second, on distal chr1, coinciding with the Sle1 locus implicated in susceptibility to lupus-like autoimmune disease, a contribution by the fcgr2 candidate gene was excluded. Two other regions, on chr12 and chr18 may also contribute to susceptibility to serum-transferred arthritis, albeit to a more limited degree. The contributions of these loci are additive, but gene dosage effects at the C5 locus are such that it largely dominates. The clarity of these results argues that our focus on the terminal effector phase of arthritis in the K/B×N model will bear fruit.
Nephritis and Chemotherapy of Tuberculosis
Authors: William J. Stone
Journal: JAMA (1977)

<h3>To the Editor.—</h3> We have recently reported three patients with acute diffuse interstitial nephritis related to the chemotherapy of tuberculosis.<sup>1</sup>These cases were quite similar to the case reported by Gabow et al (235: 2517, 1976), but only one patient received rifampin. I believe that the conclusions of Gabow et al, which incriminated rifampin alone in the illness of their patient, are not totally justified, given our present state of knowledge of the pathogenesis of interstitial nephritis. In their patient, as in two of our own, it is at least possible that isoniazid or ethambutol or both may have caused or contributed to the renal lesion. The moral of all this is that current therapeutic regimens for tuberculosis do have nephrotoxic side effects that, although probably uncommon, are underdiagnosed.
Weight Loss, Glycemic Control, and Changes in Cardiovascular Biomarkers in Patients With Type 2 Diabetes Receiving Incretin Therapies or Insulin in a Large Cohort Database
Authors: Edward S. Horton, Cheryl Silberman, Keith L. Davis, Rachele Berria
Journal: Diabetes Care (2010)

OBJECTIVE Weight loss in patients with type 2 diabetes can improve glycemic control, lower blood pressure, and improve dyslipidemia. Glucagon-like peptide (GLP-1) receptor agonists are associated with weight loss and have potentially beneficial effects on cardiovascular risk biomarkers; however, there is limited information to indicate whether these effects remain outside of clinical trials. RESEARCH DESIGN AND METHODS Medical records from the General Electric Centricity research database were analyzed retrospectively to evaluate the relationship between weight loss and glycemic control and changes in blood pressure and lipids in patients with type 2 diabetes initiating therapy with exenatide, sitagliptin, or insulin. Baseline and follow-up (90–365 days after the index date) for weight, A1C, fasting blood glucose (FBG), blood pressure, triglycerides, and LDL, HDL, and total cholesterol were assessed. RESULTS A total of 6,280, 5,861, and 32,398 patients receiving exenatide, sitagliptin, or insulin, respectively, were included in the analysis. Exenatide-treated patients lost a mean ± SD of 3.0 ± 7.33 kg, sitagliptin-treated patients lost 1.1 ± 5.39 kg, and insulin-treated patients gained 0.6 ± 9.49 kg. There was a significant association between weight loss and a reduction in A1C and FBG with exenatide only and a reduction in blood pressure for all therapies. Weight loss was associated with some improvements in lipids, primarily in the GLP-1 receptor agonist group, with little association in the insulin group. CONCLUSIONS Weight reduction with GLP-1 receptor agonists was associated with a shift toward a more favorable cardiovascular risk profile. Outcome trials are needed to determine whether improvement in biomarkers translates into a reduction in cardiovascular events in patients with type 2 diabetes.
Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling
Authors: Sang-Hoon Sin, Debasmita Roy, Ling Wang, Michelle R. Staudt, Farnaz D. Fakhari, Dhavalkumar D. Patel, David Henry, William J. Harrington, Blossom A. Damania, Dirk P. Dittmer
Journal: Blood (2006)
Beyond rationality: Rigor without mortis in game theory
Authors: Andrew M. Colman
Journal: Behavioral and Brain Sciences (2003)

Psychological game theory encompasses formal theories designed to remedy game-theoretic indeterminacy and to predict strategic interaction more accurately. Its theoretical plurality entails second-order indeterminacy, but this seems unavoidable. Orthodox game theory cannot solve payoff-dominance problems, and remedies based on interval-valued beliefs or payoff transformations are inadequate. Evolutionary game theory applies only to repeated interactions, and behavioral ecology is powerless to explain cooperation between genetically unrelated strangers in isolated interactions. Punishment of defectors elucidates cooperation in social dilemmas but leaves punishing behavior unexplained. Team reasoning solves problems of coordination and cooperation, but aggregation of individual preferences is problematic.
Epidemic of Pediatric Deaths From Acute Renal Failure Caused by Diethylene Glycol Poisoning
Authors: O'Brien Kl, Selanikio Jd, Hecdivert C, Placide Mf, Louis M, Barr Db, Barr, Hospedales Cj, Lewis Mj, Schwartz B, Philen Rm, St Victor S, Espindola J, Needham Ll, Denerville K
Journal: JAMA (1998)

Contaminated pharmaceutical products can result in substantial morbidity and mortality and should be included in the differential diagnosis of deaths of unknown origin.To investigate an outbreak of deaths among children from acute renal failure in Haiti to determine the etiology and institute control measures.Case-control study, cohort study, and laboratory toxicologic evaluation.Pediatric population of Haiti.Cases were defined as Haitian residents younger than 18 years with idiopathic anuria or severe oliguria for 24 hours or longer. Febrile hospitalized children without renal failure were enrolled as control subjects.The odds of exposure to suspected etiologic agents among cases and controls.We identified 109 cases of acute renal failure among children. The clinical syndrome included renal failure, hepatitis, pancreatitis, central nervous system impairment, coma, and death. Of 87 patients with follow-up information who remained in Haiti for treatment, 85 (98%) died; 3 (27%) of 11 patients transported to the United States for intensive care unit management died before hospital discharge. A locally manufactured acetaminophen syrup was highly associated with disease (odds ratio, 52.7; 95% confidence interval, 15.2-197.2). Diethylene glycol (DEG) was found in patients' bottles in a median concentration of 14.4%. The median estimated toxic dose of DEG was 1.34 mL/kg (range, 0.22-4.42 mL/kg). Glycerin, a raw material imported to Haiti and used in the acetaminophen formulation, was contaminated with 24% DEG.An epidemic of severe systemic toxicity and deaths from DEG-contaminated acetaminophen syrup occurred in Haiti. Good manufacturing practice regulations should be used by all pharmaceutical manufacturers to prevent such tragedies.
Sickle erythrocyte adherence to vascular endothelium. Morphologic correlates and the requirement for divalent cations and collagen-binding plasma proteins.
Authors: N Mohandas, E Evans
Journal: Journal of Clinical Investigation (1985)

Increased adherence of sickle erythrocytes to vascular endothelium has been suggested by Hebbel and his colleagues to play a role in vasocclusive events of sickle cell disease. To define the role of cell membrane changes and plasma factors in cell adherence, a micropipette technique previously developed by us to obtain a direct, quantitative measure of cell adherence was used to evaluate the adhesivity of different morphologic classes of sickle cells to endothelial cells in various suspending media. Irregularly shaped, deformable sickle cells were four- to fivefold more adherent than discoid sickle cells, whereas rigid irreversibly sickled cells were least adherent. Sickle erythrocytes adhered to endothelial cells when suspended in autologous citrated or heparinized plasma but were totally nonadherent when suspended in autologous EDTA plasma. Removal of the divalent cation chelator and addition of calcium to EDTA plasma restored its ability to promote adhesion, implying an absolute requirement for divalent cations in sickle cell adherence. Sickle cells also did not adhere to endothelial cells in protein-free media containing divalent cations, suggesting an additional requirement for plasma proteins. Removal of collagen-binding proteins from citrated sickle plasma resulted in a three- to fivefold reduction in its ability to promote cell adhesion, suggesting an important role for these plasma proteins in sickle cell adherence. The results of this study imply that sickle cell adherence to vascular endothelium is a complex process in which temporal changes in the numbers of cells identified to be most adhesive and the plasma concentration of protein(s) involved in the adhesive process determine the extent of in vivo sickle cell adherence.
Population structure in the American oyster as inferred by nuclear gene genealogies
Authors: M. P. Hare, J. C. Avise
Journal: Molecular Biology and Evolution (1998)

Multiple haplotypes from each of three nuclear loci were isolated and sequenced from geographic populations of the American oyster, Crassostrea virginica. In tests of alternative phylogeographic hypotheses for this species, nuclear gene genealogies constructed for these haplotypes were compared to one another, to a mitochondrial gene tree, and to patterns of allele frequency variation in nuclear restriction site polymorphisms (RFLPs) and allozymes. Oyster populations from the Atlantic versus the Gulf of Mexico are not reciprocally monophyletic in any of the nuclear gene trees, despite considerable genetic variation and despite large allele frequency differences previously reported in several other genetic assays. If these populations were separated vicariantly in the past, either insufficient time has elapsed for neutral lineage sorting to have achieved monophyly at most nuclear loci, or balancing selection may have inhibited lineage extinction, or secondary gene flow may have moved haplotypes between regions. These and other possibilities are examined in light of available genetic evidence, and it is concluded that no simple explanation can account for the great variety of population genetic patterns across loci displayed by American oysters. Regardless of the source of this heterogeneity, this study provides an empirical demonstration that different sequences of DNA within the same organismal pedigree can have quite different phylogeographic histories.
HLA-DR alleles differ in their ability to present staphylococcal enterotoxins to T cells.
Authors: A Herman, G Croteau, R P Sekaly, J Kappler, P Marrack
Journal: The Journal of Experimental Medicine (1990)

Staphylococcal enterotoxins (SEs) have been shown to bind to major histocompatibility complex (MHC) class II proteins and stimulate T cells in a V beta-specific manner, and these V beta specificities for various SEs have been well documented in mice and humans. This study was undertaken in order to examine the ability of human class II molecules to present SEs to human and murine T cell hybridomas. Using a panel of transfectants expressing individual HLA class II antigens, we have shown that HLA-DR alleles differ in their ability to bind and present SEs. Since the HLA-DR proteins share a common alpha chain, these results indicate that the polymorphic beta chain plays an important role in SE binding and presentation to T cells. In addition, we have shown that human class II isotypes markedly differ in their ability to present SEs. The results of this study should provide information on the region of MHC class II molecules that interacts with foreign, and perhaps self, super-antigens.
CHILDREN’S HEALTH: School Siting: EPA Says Location Matters
Authors: Bob Weinhold
Journal: Environmental Health Perspectives (2010)

Scented Products Emit a Bouquet of VOCsA survey of selected scented consumer goods showed the products emitted more than 100 volatile organic compounds (VOCs), including some that are classified as toxic or hazardous by federal laws. 1 Even products advertised as "green," "natural," or "organic" emitted as many hazardous chemicals as standard ones.