tbuckley/cabot-search huggingface dataset:
Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative
Authors: K Visser, W Katchamart, E Loza, J A Martinez-Lopez, C Salliot, J Trudeau, C Bombardier, L Carmona, D van der Heijde, J W J Bijlsma, D T Boumpas, H Canhao, C J Edwards, V Hamuryudan, T K Kvien, B F Leeb, E M Martin-Mola, H Mielants, U Muller-Ladner, G Murphy, M Ostergaard, I A Pereira, C Ramos-Remus, G Valentini, J Zochling, M Dougados
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objectives:</h3> To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. <h3>Methods:</h3> 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007–8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005–7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. <h3>Results:</h3> A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. <h3>Conclusions:</h3> Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.
Apolipoproteins AI, AII, and CI stimulate placental lactogen release from human placental tissue. A novel action of high density lipoprotein apolipoproteins.
Authors: S Handwerger, S Quarfordt, J Barrett, I Harman
Journal: Journal of Clinical Investigation (1987)

High density lipoproteins (HDL) stimulated a dose-dependent increase in the release of placental lactogen (hPL) from human placental explants. The stimulation was not prevented by delipidation of HDL but was completely blocked by tryptic digestion. Delipidated apolipoproteins (Apo) AI, AII, and CI also stimulated hPL release but other apolipoproteins were without effect. HDL and Apo CI had no effects on the release of luteinizing hormone and follicle-stimulating hormone from rat pituitary cells or the release of prolactin from human decidual cells. Because placental cells have specific HDL receptors and plasma HDL concentrations increase during pregnancy, these results strongly suggest a role for HDL in the regulation of hPL release during pregnancy possibly independent of their usual role in plasma lipid transport.
ACUTE RENAL FAILURE: Role of Dialysis Membrane Biocompatibility
Authors: Manuel Pascual, MD, Rita D. Swinford, MD, Nina Tolkoff-Rubin, MD
Journal: Annual Review of Medicine (1997)

▪ Abstract Recent clinical studies of acute renal failure in adults have focused attention on the biocompatibility of the dialysis membrane as a possible factor influencing patient morbidity and mortality. In this article, we review the concept of dialysis membrane biocompatibility and highlight the difficulty of finding an ideal definition. We then expand on the possible roles of complement and neutrophil activation by dialysis membranes, which may prolong the recovery from acute renal failure. The results of several clinical studies analyzing the impact of dialysis membranes on the course and outcome of acute renal failure are discussed. Finally, the possible relevance of biocompatibility in continuous renal replacement therapies is emphasized.
Skeletal muscle effects of electrostimulation after COPD exacerbation: a pilot study
Authors: A. Abdellaoui, C. Préfaut, F. Gouzi, A. Couillard, M. Coisy-Quivy, G. Hugon, N. Molinari, T. Lafontaine, O. Jonquet, D. Laoudj-Chenivesse, M. Hayot
Journal: European Respiratory Journal (2011)

Muscle dysfunction is a major problem in chronic obstructive pulmonary disease (COPD), particularly after exacerbations. We thus asked whether neuromuscular electrostimulation (NMES) might be directly useful following an acute exacerbation and if such a therapy decreases muscular oxidative stress and/or alters muscle fibre distribution. A pilot randomised controlled study of NMES lasting 6 weeks was carried out in 15 in-patients (n=9 NMES; n=6 sham) following a COPD exacerbation. Stimulation was delivered to the quadriceps and hamstring muscles (35 Hz). Primary outcomes were quadriceps force and muscle oxidative stress. At the end of the study, quadriceps force improvement was statistically different between groups (p=0.02), with a significant increase only in the NMES group (median (interquartile range) 10 (4.7-11.5) kg; p=0.01). Changes in the 6-min walking distance were statistically different between groups (p=0.008), with a significant increase in the NMES group (165 (125-203) m; p=0.003). NMES did not lead to higher muscle oxidative stress, as indicated by the decrease in total protein carbonylation (p=0.02) and myosin heavy chain carbonylation (p=0.01) levels. Finally, we observed a significant increase in type I fibre proportion in the NMES group. Our study shows that following COPD exacerbation, NMES is effective in counteracting muscle dysfunction and decreases muscle oxidative stress.
Measuring participation in people with spondyloarthritis using the social role participation questionnaire
Authors: Aileen M Davis, Marvilyn P Palaganas, Elizabeth M Badley, Dafna D Gladman, Robert D Inman, Monique A Gignac
Journal: Annals of the Rheumatic Diseases (2011)

Objectives People with spondyloarthritis (SpA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) have identified the importance of understanding how their disease and its treatment impacts on their social roles. This requires a reliable and valid standardised measure, and this study evaluates these measurement properties of the Social Role Participation Questionnaire (SRPQ). Methods 109 participants (44 with AS, 65 with PsA) completed questionnaires on demographics, participation measures (SRPQ, Keele Assessment of Participation (KAP), Late Life Disability Instrument (LLDI)), disease severity (physician global) and activity (pain, fatigue, Bath Ankylosing Spondylitis Disease Activity Index), psychological measures (depressive symptoms (Hospital Anxiety and Depression Scale), Illness Intrusiveness)) and function (Health Assessment Questionnaire, Bath Ankylosing Spondylitis Functional Index). After testing scaling properties, test-retest reliability of the SRPQ was evaluated using intraclass correlation coefficients (ICC) and hypotheses of construct validity were evaluated using correlation coefficients. Results Patients with AS had a mean age of 40 years and 65% were male, whereas patients with PsA had a mean age of 53 years and 63% were male. Although there were some differences between AS and PsA participants in their social role participation, scaling properties were good for both groups. ICCs were &gt;0.90 for the satisfaction subscales of the SRPQ. For construct validity, SRPQ satisfaction subscales were moderately correlated with the KAP and LLDI (0.64–0.78), and less satisfaction was associated with higher disease severity and activity, more depressive symptoms, more illness intrusiveness and more disability (coefficients −0.67 to −0.88). Conclusion Social role participation is an important concept for people with SpA, and the SRPQ is a reliable and valid measure for use with people with AS and PsA.
Disease-associated human histocompatibility leukocyte antigen determinants in patients with seropositive rheumatoid arthritis. Functional role in antigen-specific and allogeneic T cell recognition.
Authors: C M Weyand, J J Goronzy
Journal: Journal of Clinical Investigation (1990)

The susceptibility to develop seropositive rheumatoid arthritis (RA) has been linked to specific genomic polymorphisms within the HLA complex. Two different haplotypes have been associated with the disease, HLA-DR1 and HLA-DR4. To investigate the link between such phenotypic disease associations and potential immune mechanisms we used alloreactive and antigen-specific human T cell clones. Here we describe a panel of alloreactive T cell clones directed to polymorphic determinants encoded by the third hypervariable region (hvr) of the HLA-DR beta 1-chain. T cell determinants defined by these clones are shared among HLA-DR1, HLA-Dw4, HLA-Dw13, HLA-Dw14, and HLA-Dw15, and are frequent in a population of RA patients. To study the role of such disease-associated epitopes in antigen-restricted T cell recognition we generated T cell clones from RA patients specific for mycobacterial antigens, Epstein-Barr virus antigens, and tetanus toxoid. In all three antigenic systems T cell clones were restricted to either HLA-DR1 or HLA-DR4. These data suggest that the polymorphisms within the first and second hvr of the HLA-DR beta 1-chain that are distinct in HLA-DR1 and HLA-DR4 and not associated with the disease are crucially involved in the recognition of antigens. Polymorphic determinants encoded by the third hvr are shared among disease-associated haplotypes and may function to mediate the interaction of alloreactive T cell receptor molecules with the HLA complex.
Megakaryocyte biology and related disorders
Authors: L. Pang
Journal: Journal of Clinical Investigation (2005)

Platelets, derived from megakaryocytes, have an essential role in thrombosis and hemostasis. Over the past 10 years, a great deal of new information has been obtained concerning the various aspects of hematopoiesis necessary to maintain a steady-state platelet level to support physiologic hemostasis. Here we discuss the differentiation of HSCs into megakaryocytes, with emphasis on the key cytokine signaling pathways and hematopoietic transcription factors. Recent insight into these processes elucidates the molecular bases of numerous acquired and inherited hematologic disorders. It is anticipated that the growing knowledge in these areas may be exploited for new therapeutic strategies to modulate both platelet numbers and their thrombogenicity.
A divided "elephant" under Labour?
Authors: P. Johnston
Journal: BMJ (1985)

The Department of Health and Social Security, housed in that architectural masterpiece in the Elephant and Castle, is an unwieldy brute.Its titular and political head, the Secretary of State, Norman Fowler, will inevitably be hard pressed to keep an eye on everything that goes on in his domain.Immersed as he now is, and has been for nearly two years, in the Thatcher government's wholesale reform of the social security system, it is the health side of his portfolio that gets the least of his attention.But a politician to his shoelaces, Mr Fowler will delegate responsibility only up to a point.Although health matters are the primary jurisdiction of the minister, Barney Hayhoe, his decisions and announcements have the imprimatur of the boss.Spare a thought then for Labour's health and social services team, which has to shadow this massive department.They have no vast battalion of civil servants to advise them, brief them, or shoulder the burden of alternative government.There are the unsung heroes, the research assistants and secretaries, who keep the show on the road, alerting their political masters to issues that may grab a headline or embarrass a minister.They are on hand for House of Commons question time, sitting in reserved seats on the floor of the chamber itself, hoping that their man does not make a pig's ear of it in this most public of forums.They arrive in the parliamentary press gallery laden with speeches, statistics, statements, written questions -a ton of bumf over a year, which, as they are painfully aware, is all too often destined for the wastepaper bin.
Anticardiolipin antibodies in patients with primary immunodeficiency diseases.
Authors: D Pascual-Salcedo, M C Garcia Rodriguez, M Lopez Trascasa, G Fontan
Journal: Annals of the Rheumatic Diseases (1988)

The presence of antibodies to cardiolipin was determined (by an ELISA) in 143 patients with primary immunodeficiency diseases. Thirty (21%) had raised anticardiolipin antibody levels compared with only three in 98 age matched controls. The highest prevalence of this autoantibody was found in the Wiskott-Aldrich syndrome. Patients with selective IgA deficiency also showed a high prevalence of this autoantibody (32%), while patients with severe defects in antibody production showed a low prevalence or did not have such autoantibodies. This study provides further evidence of the association between autoimmune phenomena and primary immunodeficiency diseases.
Mitotic Deregulation by Survivin in ErbB2-Overexpressing Breast Cancer Cells Contributes to Taxol Resistance
Authors: Jing Lu, Ming Tan, Wen-Chien Huang, Ping Li, Hua Guo, Ling-Ming Tseng, Xiao-hua Su, Wen-Tao Yang, Warapen Treekitkarnmongkol, Michael Andreeff, Fraser Symmans, Dihua Yu
Journal: Clinical Cancer Research (2009)

Taxol resistance remains a major obstacle to improve the benefit of breast cancer patients. Here, we studied whether overexpression of ErbB2 may lead to mitotic deregulation in breast cancer cells via up-regulation of survivin that confers Taxol resistance.ErbB2-overexpressing and ErbB2-low-expressing breast cancer cell lines were used to compare their mitotic exit rate, survivin expression level, and apoptosis level in response to Taxol. Survivin was then down-regulated by antisense oligonucleotides to evaluate its contribution to mitotic exit and Taxol resistance in ErbB2-overexpressing breast cancer cells. At last, specific PI3K/Akt and Src inhibitors were used to investigate the involvement of these two pathways in ErbB2-mediated survivin up-regulation and Taxol resistance.We found that ErbB2-overexpressing cells expressed higher levels of survivin in multiple breast cancer cell lines and patient samples. ErbB2-overexpressing cells exited M phase faster than ErbB2-low-expressing cells, which correlated with the increased resistance to Taxol-induced apoptosis. Down-regulation of survivin by antisense oligonucleotide delayed mitotic exit of ErbB2-overexpressing cells and also sensitized ErbB2-overexpressing cells to Taxol-induced apoptosis. Moreover, ErbB2 up-regulated survivin at translational level and PI3K/Akt and Src activation are involved. In addition, combination treatment of Taxol with PI3K/Akt and Src inhibitor led to increased apoptosis in ErbB2-overexpressing breast cancer cells than single treatment.Survivin up-regulation by ErbB2 is a critical event in ErbB2-mediated faster mitotic exit and contributes to Taxol resistance.
MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients
Authors: Animesh D. Pardanani, Ross L. Levine, Terra Lasho, Yana Pikman, Ruben A. Mesa, Martha Wadleigh, David P. Steensma, Michelle A. Elliott, Alexandra P. Wolanskyj, William J. Hogan, Rebecca F. McClure, Mark R. Litzow, D. Gary Gilliland, Ayalew Tefferi
Journal: Blood (2006)
Interferon gamma-1b does not improve survival for patients with idiopathic pulmonary fibrosis
Authors: A. Mackay
Journal: Thorax (2010)

Idiopathic pulmonary fibrosis (IPF) is characterised by an insidious decline in pulmonary function, progressive worsening symptoms and death, with a median survival of 2–5 years from diagnosis. A methodologically limited meta-analysis has suggested that interferon γ-1b (IFNγ-1b) might improve survival.

To test this hypothesis, the INSPIRE study group conducted a double-blind trial, randomising 826 patients with IPF to receive IFNγ-1b …
Hepatic ferritin uptake and hepatic iron
Authors: Paaul C. Adams, Luan A. Chau
Journal: Hepatology (1990)

The effect of hepatic iron on the uptake of ferritin was studied by perfusing livers from normal, iron deficient and iron–loaded rats with 125 I–labeled ferritin. Unlabeled ferritin with tracer doses of labeled ferritin in concentrations of 0.02 to 2,700 nmol/L were studied. Rats were made iron deficient by feeding an established iron–deficient diet for 3 wk. Rats were iron loaded by injection of iron dextran (50 mg/wk) for 3 wk. The mean percentage of uptake of ferritin was similar for doses ranging from 0.22 to 22.2 nmol/Lof 125 I–labeled ferritin. Uptake was minimal at 4°C. The mean Percentage uptake of ferritin was 78% ± 10% in the iron–deficient rats (mean hepatic iron = 1.5μmol/gm), 79% ± 10% in the normal animals (mean hepatic iron = 9.2 μmol/gm) and 78% ± 8% in the iron–loaded animals (mean hepatic iron = 192 μmol/gm). In this experimental system, modulation of hepatic iron did not affect uptake of ferritin, suggesting that regulation of the hepatic ferrition, suggesting that regulation of the hepatic ferritin receptor may not depend on hepatic iron content. The rapid uptakee of ferritin by the liver despite iron noregulation of non–transferrin–bound iron by hepatic iron and may play a role in the progressive iron overload seen in hemochromatosis.(HEPATOLOGY 1990; 11:805–808.)
Micrometastases in Sentinel Lymph Node in a Multicentric Study: Predictive Factors of Nonsentinel Lymph Node Involvement—Groupe Des Chirurgiens De La Federation Des Centres De Lutte Contre Le Cancer
Authors: Gilles Houvenaeghel, Claude Nos, Hervé Mignotte, Jean Marc Classe, Sylvie Giard, Philippe Rouanet, Frédérique Penault Lorca, Jocelyne Jacquemier, Valérie Jeanne Bardou
Journal: Journal of Clinical Oncology (2006)

To determine the rate of nonsentinel lymph node (NSN) involvement at axillary lymph node dissection (ALND) and predictive factors of this involvement following detection of micrometastasis in sentinel nodes (SN).We analyzed 700 observations of SN micrometastases with additional ALND with the characteristics of the patients, tumors, and SN.Involvement of SN was diagnosed 388 times by serial sections (55.4%) with standard hemoxylin and eosin staining (HES) and 312 times solely on immunohistochemical analysis (IHC; 44.6%). The accurate size of the micrometastases was indicated in 488 cases: 301 larger than 0.2 mm (61.7%) and 187 < or = 0.2 mm (38.3%). Ninety-four patients (13.4%) presented an NSN involvement with only one NSN involved in 62 cases (66%). Predictive factors of NSN involvement were in univariate analysis (pT stage [P < .000], menopausal status [P = .048], T stage [P = .006], grade [P = .013], lymphovascular invasion [LVI; P = .013], histologic tumor type [P = .017], and method of micrometastasis detection, by HES or IHC [P = .015]) and in multivariate analysis (pT stage < or = or > 20 mm [odds ratio, 2.54], micrometastases detected by HES or IHC [odds ratio,1.734], presence or absence of LVI [odds ratio, 1.706]). Micrometastasis size < or = or greater than 0.2 mm was not predictive.This study confirms the value of serial sections and the vital role played by IHC in screening for small micrometastases. Omission of additional ALND may be envisaged with minimal risk for pT1a and pT1b tumors, and pT1a-b-c tumors corresponding to tubular, colloidal, or medullar cancers.
53BP1 regulates DNA resection and the choice between classical and alternative end joining during class switch recombination
Authors: Anne Bothmer, Davide F. Robbiani, Niklas Feldhahn, Anna Gazumyan, Andre Nussenzweig, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2010)

Class switch recombination (CSR) diversifies antibodies by joining highly repetitive DNA elements, which are separated by 60-200 kbp. CSR is initiated by activation-induced cytidine deaminase, an enzyme that produces multiple DNA double-strand breaks (DSBs) in switch regions. Switch regions are joined by a mechanism that requires an intact DNA damage response and classical or alternative nonhomologous end joining (A-NHEJ). Among the DNA damage response factors, 53BP1 has the most profound effect on CSR. We explore the role of 53BP1 in intrachromosomal DNA repair using I-SceI to introduce paired DSBs in the IgH locus. We find that the absence of 53BP1 results in an ataxia telangiectasia mutated-dependent increase in DNA end resection and that resected DNA is preferentially repaired by microhomology-mediated A-NHEJ. We propose that 53BP1 favors long-range CSR in part by protecting DNA ends against resection, which prevents A-NHEJ-dependent short-range rejoining of intra-switch region DSBs.
Tissue Changes Resulting from the Injection of γ-Irradiated Cells into the Gynogenetic Teleost, Poecilia formosa
Authors: Woodhead D, Setlow Rb, Hart Rw
Journal: Cancer Research (1977)

In previous studies a clone of the gynogenetic fish, Poecilia formosa (the Amazon molly), was successfully used as a test animal to identify ultraviolet-induced damage. This work has been extended, and the fish system was used to detect damage caused by ionizing radiation. Fish cells, exposed in vitro to 250 and 500 rads, were injected into young isogenic recipients, and 9 months later the fish were examined grossly and histologically. Two of the most conspicuous changes that resulted were the development of extensive invasive thyroid hyperplasia and hypertrophy and the presence of large hemorrhages throughout the body, with an apparent reduction in the amount of hematopoietic tissue in the head kidney and spleen. We discuss the difference between the responses of the recipient fish to cells exposed to ionizing radiation and to cells exposed to ultraviolet light.
Prostaglandin E receptors in cardiac sarcolemma. Identification and coupling to adenylate cyclase.
Authors: G D Lopaschuk, M Michalak, E L Wandler, R W Lerner, T D Piscione, F Coceani, P M Olley
Journal: Circulation Research (1989)

Purified cardiac sarcolemmal membrane vesicles were used to determine if specific prostaglandin (PG) receptors are present on the myocyte. Two binding sites for PGE2 were identified in isolated bovine sarcolemmal membranes: a high-affinity site with a dissociation constant (Kd) of 0.32 nM and a maximum binding (Bmax) of 376 fmol/mg of protein and a lower-affinity site with a Kd of 3.41 nM and a Bmax of 2,112 fmol/mg of protein. In competition experiments, unlabeled PGE1 displaced [3H]PGE2 from its membrane receptor at concentrations similar to those of unlabeled PGE2. Both PGF2 alpha and PGD2 displaced [3H]PGE2 from the membrane, but only at high concentrations (greater than 10(-6) M and greater than 10(-5)M, respectively). Digestion of sarcolemmal membrane with trypsin resulted in a threefold decrease in specific [3H]PGE2 binding. Phosphorylation of the membrane with protein kinase A also decreased specific [3H]PGE2 binding. At concentrations of PGE2 that occupy the high-affinity site, sarcolemmal adenylate cyclase activity was inhibited in the presence of 5'-guanylylimidodiphosphate [Gpp(NH)p]. We conclude that the isolated cardiac sarcolemmal membrane contains a high-affinity binding site for PGE2 that is functionally coupled to adenylate cyclase. The binding site is stereospecific and probably recognizes the 9-keto,11-hydroxyl portion of the ring structure of these prostaglandins.