tbuckley/cabot-search huggingface dataset:
The fibrin-derived citrullinated peptide β60–74Cit<sub>60,72,74</sub>bears the major ACPA epitope recognised by the rheumatoid arthritis-specific anticitrullinated fibrinogen autoantibodies and anti-CCP2 antibodies
Authors: M Cornillet, M Sebbag, E Verrouil, A Magyar, F Babos, A Ruyssen-Witrand, F Hudecz, A Cantagrel, G Serre, L Nogueira
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To evaluate the proportions of rheumatoid arthritis (RA) sera containing anticitrullinated proteins autoantibodies (ACPA) reactive to α36–50Cit<sub>38,42</sub> and/or β60–74Cit<sub>60,72,74</sub>, two peptides identified as bearing the immunodominant epitopes of their major target, citrullinated fibrin. To analyse the relationships of anti-α36–50Cit<sub>38,42</sub> and anti-β60–74Cit<sub>60,72,74</sub> autoantibodies with autoantibodies reactive to the complete citrullinated human fibrinogen molecule (AhFibA) and with anti-CCP2 antibodies. <h3>Methods</h3> &nbsp;617 sera from 181 patients with established RA and 436 with non-RA rheumatic diseases were tested by ELISA for AhFibA, anti-CCP2, anti-α36–50Cit<sub>38,42</sub>, anti-β60–74Cit<sub>60,72,74</sub> autoantibodies, and by nephelometry for rheumatoid factor (RF). Diagnostic indexes, correlations and concordances between tests were analysed. Crossreactivity of anti-α36–50Cit<sub>38,42</sub> and anti-β60–74Cit<sub>60,72,74</sub> autoantibodies was assessed in competition experiments. <h3>Results</h3> At a diagnostic specificity of 95%, the diagnostic sensitivity of AhFibA (83%) was significantly higher than that of all other tests. The diagnostic sensitivity of anti-β60–74Cit<sub>60,72,74</sub> (71%) was significantly higher than that of anti-α36–50Cit<sub>38,42</sub> autoantibodies (51%) but similar to that of anti-CCP2 (74%). Titres of RF, anti-α36–50Cit<sub>38,42</sub> and anti-β60–74Cit<sub>60,72,74</sub> autoantibodies were weakly correlated with each other, whereas titres of anti-β60–74Cit<sub>60,72,74</sub> were strongly correlated with those of AhFibA (r=0.633) and anti-CCP2 (r=0.634). Anti-α36–50Cit<sub>38,42</sub> and anti-β60–74Cit<sub>60,72,74</sub> mainly corresponded to two non-crossreactive subfamilies of ACPA. More than 90% of AhFibA-positive or anti-CCP2-positive sera recognised the α36–50Cit<sub>38,42</sub> and/or the β60–74Cit<sub>60,72,74</sub> peptide. <h3>Conclusions</h3> Autoantibodies reactive to α36–50Cit<sub>38,42</sub> and β60–74Cit<sub>60,72,74</sub> form two distinct, non-overlapping subfamilies of ACPA that, together, cover practically all the ACPA reactivity to citrullinated fibrinogen and to CCP2 antigens. In established RA, anti-β60–74Cit<sub>60,72,74</sub> autoantibodies show diagnostic indexes similar to those of anti-CCP2.
Biological variability and control of movements via δλ
Authors: Charles E. Wright, Rebecca A. States
Journal: Behavioral and Brain Sciences (1995)

Abstract Three issues related to Feldman and Levin's treatment of biological variability are discussed. We question the usefulness of the indirect component of δλ. We suggest that trade-offs between speed and accuracy in aimed movements support identification of δλ, rather than λ, as a control variable. We take issue with the authors' proposal for resolving redundancy in multi-joint movements, given recent data.
Autoantibodies against triosephosphate isomerase. A possible clue to pathogenesis of hemolytic anemia in infectious mononucleosis.
Authors: K Ritter, H Brestrich, B Nellen, H Kratzin, H Eiffert, R Thomssen
Journal: The Journal of Experimental Medicine (1990)

In sera from patients with acute EBV, infection and the clinical symptoms of infectious mononucleosis antibodies of the Ig class M were found that are directed against two cellular proteins. The molecular mass of these proteins was determined to be 29 (p29) and 26 kD (p26), respectively, in SDS-PAGE. P29 was identified as part of the glycolytic enzyme triosephosphate isomerase (TPI) by comparison of the NH2-terminal amino acid sequences. A purified antibody against TPI induces a 51Cr release from human erythrocytes. Possibly, anti-TPI causes hemolysis, which is an infrequent but serious symptom of infectious mononucleosis.
Low-level laser irradiation inhibits abdominal aortic aneurysm progression in apolipoprotein E-deficient mice
Authors: L. Gavish, C. Rubinstein, A. Bulut, Y. Berlatzky, R. Beeri, D. Gilon, L. Gavish, M. Harlev, P. Reissman, S. D. Gertz
Journal: Cardiovascular Research (2009)

Increased early detection of abdominal aortic aneurysm (AAA) and the severe complications of its current treatment have emphasized the need for alternative therapeutic strategies that target pathogenetic mechanisms of progression and rupture. Recent in vitro studies from our laboratory have shown that low-level laser irradiation (LLLI) (780 nm) modifies cellular processes fundamental to aneurysm progression. The present study was designed to determine whether LLLI retards the progression of suprarenal AAA in vivo.High-frequency ultrasonography (0.01 mm resolution) was used to quantify the effect of LLLI on aneurysmatic aortic dilatation from baseline to 4 weeks after subcutaneous infusion of angiotensin II by osmotic minipumps in the apolipoprotein E-deficient mouse. At 4 weeks, seven of 15 non-irradiated, but none of the 13 LLLI, mice had aneurysmal dilatation in the suprarenal aneurysm-prone segments that had progressed to >or=50% increase in maximal cross-sectional diameter (CSD) over baseline (P = 0.005 by Fisher's exact test). The mean CSD of the suprarenal segments (normalized individually to inter-renal control segments) was also significantly lower in irradiated animals (LLLI vs. non-irradiated: 1.32 +/- 0.14 vs. 1.82 +/- 0.39, P = 0.0002 by unpaired, two-tailed t-test) with a 94% reduction in CSD at 4 weeks compared with baseline. M-mode ultrasound data showed that reduced radial wall velocity seen in non-treated was significantly attenuated in the LLLI mice, suggesting a substantial effect on arterial wall elasticity.These in vivo studies, together with previous in vitro studies from this laboratory, appear to provide strong evidence in support of a role for LLLI in the attenuation of aneurysm progression. Further studies in large animals would appear to be the next step towards testing the applicability of this technology to the human interventional setting.
PLK1 Is Transcriptionally Activated by NF-κB during Cell Detachment and Enhances Anoikis Resistance through Inhibiting β-Catenin Degradation in Esophageal Squamous Cell Carcinoma
Authors: De-Chen Lin, Yu Zhang, Qin-Jing Pan, Hai Yang, Zhi-Zhou Shi, Zhi-Hui Xie, Bo-Shi Wang, Jia-Jie Hao, Tong-Tong Zhang, Xin Xu, Qi-Min Zhan, Ming-Rong Wang
Journal: Clinical Cancer Research (2011)

To investigate the molecular mechanisms through which polo-like kinase-1 (PLK1) takes part in anoikis resistance of esophageal squamous cell carcinoma (ESCC) cells.The role of PLK1 in cell anoikis resistance was examined by ectopic gene expression and siRNA-mediated knockdown. Glutathione S-transferase pull-down and co-immunoprecipitation assays were utilized to investigate PLK1-interacting proteins. Electrophoretic mobility shift assay, chromatin immunoprecipitation, and reporter gene assays were carried out to identify the transcription factors responsible for PLK1 expression during anoikis resistance.We found that detachment of ESCC cells triggers the upregulation of PLK1. Elevated PLK1 expression contributes to protection against anoikis in cancer cells through the regulation of β-catenin expression. Moreover, we showed that, through direct binding to the PLK1 promoter, the NF-κB subunit RelA transcriptionally activates PLK1, which inhibits the ubiquitination and degradation of β-catenin. Inhibition of the NF-κB pathway restores the sensitivity of cancer cells to anoikis by downregulating PLK1/β-catenin expression. In addition, RelA gene amplification and protein overexpression was significantly correlated with PLK1 expression in ESCC tissues.Our findings suggest that upregulation of PLK1 triggered by cell detachment is regulated by RelA at the transcriptional level. PLK1 protects esophageal carcinoma cells from anoikis through modulation of β-catenin protein levels by inhibiting their degradation. Taken together, this study reveals critical mechanisms involved in the role of RelA/PLK1/β-catenin in anoikis resistance of ESCC cells.
Der f 22: A Novel Allergen From Dermatophagoides farinae That Is Encoded By A Gene Paralogous To Der f 2
Authors: F.T. Chew, K. Reginald, C.L. Tan, T.C. Ong, K.N. Wong, Y.S. Tiong, L.Y. Yit, H.S. Shang
Journal: Journal of Allergy and Clinical Immunology (2009)
Tachykinin receptor antagonists inhibit hyperpnea-induced bronchoconstriction in guinea pigs.
Authors: J Solway, B M Kao, J E Jordan, B Gitter, I W Rodger, J J Howbert, L E Alger, J Necheles, A R Leff, A Garland
Journal: Journal of Clinical Investigation (1993)

We tested the hypothesis that hyperpnea-induced bronchoconstriction (HIB) and hyperpnea-induced bronchovascular hyperpermeability (HIBVH) are mediated through stimulation of NK-1 and NK-2 receptors in guinea pigs. We first established the efficacy and selectivity of (+/-) CP-96,345 (3 mg/kg i.v.) and of SR-48,968 (300 micrograms/kg i.v.) as NK-1 and NK-2 antagonists, respectively. (+/-) CP-96,345 substantially attenuated bronchoconstriction and systemic vascular leak caused by administration of Sar9,Met(O2)11-Substance P (a specific NK-1 agonist), but had no effect upon bronchoconstriction induced by selective NK-2 stimulation with Nle10-Neurokinin A[4-10]. Conversely, SR-48,968 antagonized the bronchoconstrictor response to Nle10-NKA[4-10], right-shifting the dose-response curve by 2 log units, but had no effect on Sar9, Met(O2)11-SP-induced bronchoconstriction. Anesthetized, tracheostomized, opened-chest male Hartley guinea pigs were pretreated with (+/-) CP-96,345 (3 mg/kg i.v.), SR-48,968 (300 micrograms/kg i.v.), or their respective vehicles, and Evans blue dye (30 mg/kg i.v.) to label circulating albumin. 10 min isocapnic dry gas hyperpnea (12 ml/kg, 150 breaths/min) provoked HIB and HIBVH in vehicle-treated animals. (+/-) CP-96,345 reduced the magnitude of HIB by one-half (peak posthyperpnea RL 7.8 +/- 1.9 [SE] times prehyperpnea baseline versus 16.1 +/- 2.6, vehicle-treated; P < or = 0.0001, ANOVA); SR-48,968 blocked HIB more completely (peak posthyperpnea RL 5.1 +/- 1.7 [SE] times prehyperpnea baseline versus 19.3 +/- 2.8, vehicle-treated; P < 0.0001, ANOVA). Neither drug reduced HIBVH. We conclude that dry gas hyperpnea causes bronchoconstriction in guinea pigs through activation of tachykinin receptors. The differential effects of neurokinin receptor blockade on HIB and HIBVH demonstrate that hyperpnea-induced airflow obstruction is not primarily a consequence of hyperpnea-induced bronchovascular leak.
A weighted genetic risk score using all known susceptibility variants to estimate rheumatoid arthritis risk
Authors: Annie Yarwood, Buhm Han, Soumya Raychaudhuri, John Bowes, Mark Lunt, Dimitrios A Pappas, Joel Kremer, Jeffrey D Greenberg, Robert Plenge, Jane Worthington, Anne Barton, Steve Eyre
Journal: Annals of the Rheumatic Diseases (2013)

Background There is currently great interest in the incorporation of genetic susceptibility loci into screening models to identify individuals at high risk of disease. Here, we present the first risk prediction model including all 46 known genetic loci associated with rheumatoid arthritis (RA). Methods A weighted genetic risk score (wGRS) was created using 45 RA non-human leucocyte antigen (HLA) susceptibility loci, imputed amino acids at HLA-DRB1 (11, 71 and 74), HLA-DPB1 (position 9) HLA-B (position 9) and gender. The wGRS was tested in 11 366 RA cases and 15 489 healthy controls. The risk of developing RA was estimated using logistic regression by dividing the wGRS into quintiles. The ability of the wGRS to discriminate between cases and controls was assessed by receiver operator characteristic analysis and discrimination improvement tests. Results Individuals in the highest risk group showed significantly increased odds of developing anti-cyclic citrullinated peptide-positive RA compared to the lowest risk group (OR 27.13, 95% CI 23.70 to 31.05). The wGRS was validated in an independent cohort that showed similar results (area under the curve 0.78, OR 18.00, 95% CI 13.67 to 23.71). Comparison of the full wGRS with a wGRS in which HLA amino acids were replaced by a HLA tag single-nucleotide polymorphism showed a significant loss of sensitivity and specificity. Conclusions Our study suggests that in RA, even when using all known genetic susceptibility variants, prediction performance remains modest; while this is insufficiently accurate for general population screening, it may prove of more use in targeted studies. Our study has also highlighted the importance of including HLA variation in risk prediction models.
Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability
Authors: P. D. Cani, S. Possemiers, T. Van de Wiele, Y. Guiot, A. Everard, O. Rottier, L. Geurts, D. Naslain, A. Neyrinck, D. M. Lambert, G. G. Muccioli, N. M. Delzenne
Journal: Gut (2009)

<h3>Background and aims:</h3> Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of <i>Bifidobacterium</i> spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that prebiotic modulation of gut microbiota lowers intestinal permeability, by a mechanism involving glucagon-like peptide-2 (GLP-2) thereby improving inflammation and metabolic disorders during obesity and diabetes. <h3>Methods:</h3> Study 1: <i>ob/ob</i> mice (Ob-CT) were treated with either prebiotic (Ob-Pre) or non-prebiotic carbohydrates as control (Ob-Cell). Study 2: Ob-CT and Ob-Pre mice were treated with GLP-2 antagonist or saline. Study 3: Ob-CT mice were treated with a GLP-2 agonist or saline. We assessed changes in the gut microbiota, intestinal permeability, gut peptides, intestinal epithelial tight-junction proteins ZO-1 and occludin (qPCR and immunohistochemistry), hepatic and systemic inflammation. <h3>Results:</h3> Prebiotic-treated mice exhibited a lower plasma lipopolysaccharide (LPS) and cytokines, and a decreased hepatic expression of inflammatory and oxidative stress markers. This decreased inflammatory tone was associated with a lower intestinal permeability and improved tight-junction integrity compared to controls. Prebiotic increased the endogenous intestinotrophic proglucagon-derived peptide (GLP-2) production whereas the GLP-2 antagonist abolished most of the prebiotic effects. Finally, pharmacological GLP-2 treatment decreased gut permeability, systemic and hepatic inflammatory phenotype associated with obesity to a similar extent as that observed following prebiotic-induced changes in gut microbiota. <h3>Conclusion:</h3> We found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP-2-dependent mechanism, contributing to the improvement of gut barrier functions during obesity and diabetes.
Restoration of Normal L-Type Ca <sup>2+</sup> Channel Function During Timothy Syndrome by Ablation of an Anchoring Protein
Authors: Edward P. Cheng, Can Yuan, Manuel F. Navedo, Rose E. Dixon, Madeline Nieves-Cintrón, John D. Scott, Luis F. Santana
Journal: Circulation Research (2011)

L-type Ca(2+) (Ca(V)1.2) channels shape the cardiac action potential waveform and are essential for excitation-contraction coupling in heart. A gain-of-function G406R mutation in a cytoplasmic loop of Ca(V)1.2 channels causes long QT syndrome 8 (LQT8), a disease also known as Timothy syndrome. However, the mechanisms by which this mutation enhances Ca(V)1.2-LQT8 currents and generates lethal arrhythmias are unclear.To test the hypothesis that the anchoring protein AKAP150 modulates Ca(V)1.2-LQT8 channel gating in ventricular myocytes.Using a combination of molecular, imaging, and electrophysiological approaches, we discovered that Ca(V)1.2-LQT8 channels are abnormally coupled to AKAP150. A pathophysiological consequence of forming this aberrant ion channel-anchoring protein complex is enhanced Ca(V)1.2-LQT8 currents. This occurs through a mechanism whereby the anchoring protein functions like a subunit of Ca(V)1.2-LQT8 channels that stabilizes the open conformation and augments the probability of coordinated openings of these channels. Ablation of AKAP150 restores normal gating in Ca(V)1.2-LQT8 channels and protects the heart from arrhythmias.We propose that AKAP150-dependent changes in Ca(V)1.2-LQT8 channel gating may constitute a novel general mechanism for Ca(V)1.2-driven arrhythmias.
ANEURYSMAL VARIX OF POPLITEAL VESSELS FROM GUNSHOT WOUND
Authors: R. B. Wright
Journal: BMJ (1915)

ANEURUlY AL VARTX OF POPLtTAtL VtSSEtg.965 frequency of respiration wlichl persisted for days, and lhad iot entirely subsided upon their discharge to convalescent camI.GRoup II.-THE MIIODERRATELY SEVERE CASES.These patients were actually ill.They were cyanotic, witlh frequLent panting and painfuLl respiration, which caused tlhemi the greatest dtiscomiifort.Headachle -was very marked, and pyrexia'up to about 100' F. was conimmon for tlhree or four days.Tllhe phlysical signls varied in different parts of the clhest.In the upper part the sounds were lould, withi sibilant rlhonclli.Lower down, especially at the baclk, tllere were submucouls rt'les, indlicatin(g a "bronclhiolitis."Suell patienlts were usually drowsy, alnd tenided to get mluchl wvorse at nighlt.GRoup Ilf.-TIIE VERY SEVERE CASES.The only case of tllis group wlliclh canme uinder otur care, anid of wlhiclh -we propose to give some detailed notes togethier witlh tlle post-mzortenw findings, exhiibited signs of extrelmle poisoninig wlhich led to a fatal resuilt.The mnan was admliittedl in a senmi-comnatose condition twenty-fouce hours after being exposed to the fuLmlles.HIe -was initensely cyaniotic, respiration-rate 30 to the m-linute, puLlse 88, tlhroat dry and red1, tongue crackled and futrred.WhNlen roused-which could only be done with great dlifficulty-tlhe patient iucdicated by signs that lie had severe pain in the clhest.He was unable to coughl, anid there was muchielrattlincg with the breathing.Phlysical signs slhowed rales all over the clhest, front alnd back.The fremitus of these rales was easily palpated by the lhalnd.Thle condi_ tion was diagrnosed from thlese signs as acute ptulmonary odcema following, exposure to irritant f ules.Tlle blood pressure appeared to be raised, tlhough apparatus for verifying this was not at our disposal.Bleedina was resorted to, and 12 oz. of blood were withdrawn-l from the median basilic vein at the elbow.The intenselv dlark colour of the bloodl anid its reinarhable rapidlity of clotting Nyere the special feattures noted, and the latter conditioni micade tile operation very tediotus ancd difficult.The patient seerned to be relieved for a timiie but never regained con- sciouisness, anid died in twenty-four hlours frorn tlle time of hiis admission, and forty-eight hours in all fronm the time of beina exposed to the fumes.Oxygen was administered throtuglhout without any benefit.Postural treatment resulted in large quLantities of frothy secretion poturing otLt of the nose and mouth, but at no time -was the patient able to expectorate tllis for himself.Post-m?ortemn Fxam7iination.-The bocly was that of a moderately developed adult man.There were no external signis of initerest.Rigor mortis was comnplete two lhours after death.Examination of tlle chest showed very firm old pleuritic adhesions between the left lung and the chest wall.The lungs were fully expanded, crepitant through-
STUDIES ON HUMAN ANTIBODIES
Authors: Carlos Moreno, Elvin A. Kabat
Journal: The Journal of Experimental Medicine (1969)

Human antibodies to blood group A substance were purified by absorption on columns of insoluble polyleucyl hog blood group A + H substance and eluted first with N-acetylgalactosamine and then with an A active reduced pentasaccharide AR(L)0.52. The gammaM and gammaG antibodies in these eluates were separated by density gradient centrifugation. The antibodies were studied for their relative capacities to be inhibited by various blood group A active oligosaccharides. Antibodies eluted by the N-acetylgalactosamine could be inhibited by N-acetylgalactosamine, as well as by lower concentrations of A active tri- and pentasaccharides, while those eluted by the pentasaccharide AR(L)0.52 could only be inhibited by the two oligosaccharides, but not by N-acetylgalactosamine, indicating that the N-acetylgalactosamine eluate had more antibodies with smaller size combining sites than the AR(L)0.52 eluate. Measurements by equilibrium dialysis gave values ranging from 2 x 10(3) to 1 x 10(5)M(-1) and the values obtained with the AR(L)0.52 eluate were somewhat higher than those with the GalNAc eluate. Only one of three anti-A sera had gammaM anti-A in the AR(L)0.52 eluate, while all three had gammaM in the N-acetylgalactosamine eluate. Data on the precipitating, hemagglutinating, complement fixing, hemolytic properties of the eluted antibodies, and of their content of kappa and lambda light chains are given.
A study of changes in the spine in weight lifters and other athletes.
Authors: N. D. Aggrawal, R. Kaur, S. Kumar, D. N. Mathur
Journal: British Journal of Sports Medicine (1979)

The present study was undertaken in sportsmen of those groups of sports activities where weight training exercises constitute a major part of the training. Two groups consisting of 25 weight-lifters and 25 track and field athletes were studied to find out the effect of sports activities and lifting weights on the spine. 84% weight-lifters and 72% track and field athletes suffered from varying abnormalities. Incidence of backache in 25 weight-lifters was 40% and in 25 track and field athletes 48%. Radiological changes were more common in weight-lifters (84%) than in athletes (72%). Reduction in lumbar lordosis was found in three cases (12%) in both the groups. Obtuse angle deformity of vertebral margins was found in 11 cases (44%) amongst weight-lifters and six cases (24%) amongst athletes. Osteophytic formation was found in six cases (24%) in weight-lifters and four cases (16%) in athletes. Schmorl's node were noticed in five cases (20%) amongst weight-lifters and seven cases (28%) amongst athletes. The incidences of spondylosis and Schmorl's node were found only in those cases who had been doing weight training exercises for more than four years.
Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Long-Term Treatment of Symptomatic Venous Thromboembolism: Is There Any Difference in Cancer-Related Mortality?
Authors: Gianluigi Ferretti, Emilio Bria, Diana Giannarelli, Paolo Carlini, Alessandra Felici, Mario Mandala, Paolo Papaldo, Cecilia Nistico, Alessandra Fabi, Federica Cuppone, Alain Gelibter, Edmondo Terzoli, Francesco Cognetti
Journal: Journal of Clinical Oncology (2005)
Epidemiology of invasive cutaneous melanoma
Authors: R.M. MacKie, A. Hauschild, A.M.M. Eggermont
Journal: Annals of Oncology (2009)

Data are presented on the current incidence of melanoma with recent and predicted future trends illustrating a likely continuing increase in incidence. Risk factors for developing melanoma are discussed, including current known melanoma susceptibility genes. Phenotypic markers of high-risk subjects include high counts of benign melanocytic naevi. Other risk factors considered include exposure to natural and artificial ultraviolet radiation, the effect of female sex hormones, socioeconomic status, occupation, exposure to pesticides and ingestion of therapeutic drugs including immunosuppressives and non-steroidal anti-inflammatory drugs. Aids to earlier diagnosis are considered, including public education, screening and use of equipment such as the dermatoscope. Finally, the current pattern of survival and mortality is described.