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Anti-Topoisomerase I Antibody

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61. Phase I randomized study of KHK4083, an anti-OX40 monoclonal antibody, in patients with mild to moderate plaque psoriasis. (PubMed)

Phase I randomized study of KHK4083, an anti-OX40 monoclonal antibody, in patients with mild to moderate plaque psoriasis. OX40 (CD134) is expressed in lesional but not healthy skin of patients with psoriasis. KHK4083 is a fully human monoclonal antibody against OX40.The primary aim of this first-in-human phase 1 study was to determine the safety and tolerability of ascending single doses of KHK4083 in patients with mild to moderate plaque psoriasis. Secondary aims were to determine (...) , and 1.0 mg/kg SC.There were no severe or serious adverse events (AEs), or discontinuations because of AEs. The most frequent treatment-related AEs in the 55 patients who received KHK4083 were mild or moderate chills (9.1%), and infusion/injection site reactions (7.3%). No clinically meaningful or dose-related changes from baseline in laboratory values, vital signs, ECG recordings or physical examinations were observed. Some KHK4083 recipients (10/54) developed anti-KHK4083 antibodies following

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2017 Journal of the European Academy of Dermatology and Venereology

62. Live Birth Pregnancy Outcome after First In Vitro Fertilization Treatment in a Patient with Systemic Lupus Erythematosus and Isolated High Positive IgA Anti-β2glycoprotein I Antibodies: A Case Report (PubMed)

Live Birth Pregnancy Outcome after First In Vitro Fertilization Treatment in a Patient with Systemic Lupus Erythematosus and Isolated High Positive IgA Anti-β2glycoprotein I Antibodies: A Case Report IgA anti-β2glycoprotein I antibodies (IgA-anti-β2GPI) seems to be the most prevalent isotype in patients with Systemic Lupus Erythematosus (SLE) with a significant association to thrombotic events. Both SLE and antiphospholipid syndrome (APS) can be associated with implantation failure, fetal loss (...) and obstetric complications. Recent reports highlight the clinical value of IgA-anti-β2GPI determination in supporting in vitro fertilization (IVF) treatment and IVF pregnancy outcomes. We report a 36-year-old female diagnosed with SLE, endometriosis and unexplained infertility. Conventional APS markers were consistently negative: anti-cardiolipin (aCL) and anti-β2GPI: IgG/IgM. She was then tested with reports of repeatedly high IgA-anti-β2GPI and tested positive from 2014 after IgA (aCL; anti-β2GPI) were

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2017 Open Medicine

63. Can anti-bothropstoxin-I antibodies discriminate between Bothrops jararaca and Bothrops jararacussu venoms? (PubMed)

Can anti-bothropstoxin-I antibodies discriminate between Bothrops jararaca and Bothrops jararacussu venoms? Snakes of the genus Bothrops, popularly known as pit vipers, are responsible for most cases of snakebite in Brazil. Within this genus, Bothrops jararacussu and B. jararaca deserve special attention due to the severity of their bites and for inhabiting densely populated areas. Regarding the treatment of snakebites by Bothrops jararacussu, questions have been raised about the effectiveness (...) studies.First, we produced a species-specific polyclonal antibody - a potential biomarker of Bothrops jararacussu venom - against bothropstoxin-I (BthTx-I), which is also found in smaller quantities in the venoms of B. jararaca from southern Brazil.Polyclonal antibodies against bothropstoxin-I could be separated into several species-specific immunoglobulins. Then, aiming to develop a system of safe and standardized immunoassay, we produced monoclonal antibodies. Seven hybridomas were obtained. Five of them

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2017 The journal of venomous animals and toxins including tropical diseases

64. Upregulation of HLA Class I Expression on Tumor Cells by the Anti-EGFR Antibody Nimotuzumab (PubMed)

Upregulation of HLA Class I Expression on Tumor Cells by the Anti-EGFR Antibody Nimotuzumab Defining how epidermal growth factor receptor (EGFR)-targeting therapies influence the immune response is essential to increase their clinical efficacy. A growing emphasis is being placed on immune regulator genes that govern tumor - T cell interactions. Previous studies showed an increase in HLA class I cell surface expression in tumor cell lines treated with anti-EGFR agents. In particular, earlier (...) studies of the anti-EGFR blocking antibody cetuximab, have suggested that increased tumor expression of HLA class I is associated with positive clinical response. We investigated the effect of another commercially available anti-EGFR antibody nimotuzumab on HLA class I expression in tumor cell lines. We observed, for the first time, that nimotuzumab increases HLA class I expression and its effect is associated with a coordinated increase in mRNA levels of the principal antigen processing

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2017 Frontiers in pharmacology

65. Influence of type I IFN signaling on anti-MOG antibody-mediated demyelination (PubMed)

Influence of type I IFN signaling on anti-MOG antibody-mediated demyelination Antibodies with specificity for myelin oligodendrocyte glycoprotein (MOG) are implicated in multiple sclerosis and related diseases. The pathogenic importance of anti-MOG antibody in primary demyelinating pathology remains poorly characterized.The objective of this study is to investigate whether administration of anti-MOG antibody would be sufficient for demyelination and to determine if type I interferon (IFN (...) ) signaling plays a similar role in anti-MOG antibody-mediated pathology, as has been shown for neuromyelitis optica-like pathology.Purified IgG2a monoclonal anti-MOG antibody and mouse complement were stereotactically injected into the corpus callosum of wild-type and type I IFN receptor deficient mice (IFNAR1-KO) with and without pre-established experimental autoimmune encephalomyelitis (EAE).Anti-MOG induced complement-dependent demyelination in the corpus callosum of wild-type mice and did not occur

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2017 Journal of neuroinflammation

66. A phase I trial of the trifunctional anti Her2 × anti CD3 antibody ertumaxomab in patients with advanced solid tumors. (PubMed)

A phase I trial of the trifunctional anti Her2 × anti CD3 antibody ertumaxomab in patients with advanced solid tumors. Ertumaxomab (ertu) is a bispecific, trifunctional antibody targeting Her2/neu, CD3 and the Fcγ-receptors I, IIa, and III forming a tri-cell complex between tumor cell, T cell and accessory cells.Patients (pts) with Her2/neu (1+/SISH positive, 2+ and 3+) expressing tumors progressing after standard therapy were treated to investigate safety, tolerability and preliminary efficacy

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2016 BMC Cancer

67. <i>TP53</i>, <i>STK11</i> and <i>EGFR</i> Mutations Predict Tumor Immune Profile and the Response to anti-PD-1 in Lung Adenocarcinoma. (PubMed)

<i>TP53i>, <i>STK11i> and <i>EGFRi> Mutations Predict Tumor Immune Profile and the Response to anti-PD-1 in Lung Adenocarcinoma. Purpose: By unlocking antitumor immunity, antibodies targeting programmed cell death 1 (PD-1) exhibit impressive clinical results in non-small cell lung cancer, underlining the strong interactions between tumor and immune cells. However, factors that can robustly predict long-lasting responses are still needed.Experimental Design: We performed in-depth immune (...) (PFS: HR = 0.32; 95% CI, 0.16-0.63, P < 0.001) was observed in anti-PD-1-treated patients harboring TP53-mut/STK11-EGFR-WT tumors. This clinical benefit was even more remarkable in patients with associated strong PD-L1 expression.Conclusions: Our study reveals that different combinations of TP53, EGFR, and STK11 mutations, together with PD-L1 expression by tumor cells, represent robust parameters to identify best responders to PD-1 blockade. Clin Cancer Res; 24(22); 5710-23. ©2018 AACR.©2018

2018 Clinical Cancer Research

68. A Potential of an Anti-HTLV-I gp46 Neutralizing Monoclonal Antibody (LAT-27) for Passive Immunization against Both Horizontal and Mother-to-Child Vertical Infection with Human T Cell Leukemia Virus Type-I (PubMed)

A Potential of an Anti-HTLV-I gp46 Neutralizing Monoclonal Antibody (LAT-27) for Passive Immunization against Both Horizontal and Mother-to-Child Vertical Infection with Human T Cell Leukemia Virus Type-I Although the number of human T-cell leukemia virus type-I (HTLV-I)-infected individuals in the world has been estimated at over 10 million, no prophylaxis vaccines against HTLV-I infection are available. In this study, we took a new approach for establishing the basis of protective vaccines (...) against HTLV-I. We show here the potential of a passively administered HTLV-I neutralizing monoclonal antibody of rat origin (LAT-27) that recognizes epitopes consisting of the HTLV-I gp46 amino acids 191-196. LAT-27 completely blocked HTLV-I infection in vitro at a minimum concentration of 5 μg/mL. Neonatal rats born to mother rats pre-infused with LAT-27 were shown to have acquired a large quantity of LAT-27, and these newborns showed complete resistance against intraperitoneal infection with HTLV-I

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2016 Viruses

69. Clinical indications, image acquisition and data interpretation for white blood cells and anti-granulocyte monoclonal antibody scintigraphy

-labeled anti-granulocyte monoclonal antibody fragment.JNuclMed.1994;35(9):1436–43. 12. Gratz S, Reize P, Kemke B, Kampen WU, Lusteri M, Hoffken H. TargetingofosteomyelitiswithIgGandFab’ monoclonal antibod- ies labeled with [99mTc]: kinetic evaluations. Q J Nucl Med Mol Imaging.2014;60:413–23. 13. Palestro CJ, Mehta HH, Patel M, Freeman SJ, Harrington WN, Tomas MB, et al. Marrow versus infection in the Charcot joint: indium-111 leukocyte and technetium-99msulfur colloid scintigra- phy.JNuclMed.1998;39 (...) Clinical indications, image acquisition and data interpretation for white blood cells and anti-granulocyte monoclonal antibody scintigraphy GUIDELINES Clinical indications, image acquisition and data interpretation for white blood cells and anti-granulocyte monoclonal antibody scintigraphy: an EANM procedural guideline A.Signore 1 & F.Jamar 2 & O.Israel 3 & J.Buscombe 4 & J.Martin-Comin 5 & E.Lazzeri 6 Received: 27 April 2018 /Accepted: 6 May 2018 # The Author(s) 2018 Abstract Introduction

2018 European Association of Nuclear Medicine

70. <i>In vivo</i> pathogenicity of IgG from patients with anti-SRP or anti-HMGCR autoantibodies in immune-mediated necrotising myopathy. (PubMed)

<i>In vivoi> pathogenicity of IgG from patients with anti-SRP or anti-HMGCR autoantibodies in immune-mediated necrotising myopathy. In autoimmunity, autoantibodies (aAb) may be simple biomarkers of disease or true pathogenic effectors. A form of idiopathic inflammatory myopathy associated with anti-signal recognition particle (SRP) or anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) aAb has been individualised and is referred to as immune-mediated necrotising myopathy (IMNM). The level (...) of aAb correlates with IMNM activity and disease may respond to immunosuppression, suggesting that they are pathogenic. We aimed to evaluate the pathogenicity of IgG from patients with anti-SRP or anti-HMGCR aAb in vivo by developing the first mouse model of IMNM.IgG from patients suffering from anti-SRP or anti-HMGCR associated IMNM were passively transferred to wild-type, Rag2-/- or complement C3-/- mice. Muscle deficiency was evaluated by muscle strength on electrostimulation and grip test

2018 Annals of the Rheumatic Diseases

71. Topoisomerases I and III inhibit R-loop formation to prevent unregulated replication in the chromosomal Ter region of Escherichia coli (PubMed)

Topoisomerases I and III inhibit R-loop formation to prevent unregulated replication in the chromosomal Ter region of Escherichia coli Type 1A topoisomerases (topos) are the only ubiquitous topos. E. coli has two type 1A topos, topo I (topA) and topo III (topB). Topo I relaxes negative supercoiling in part to inhibit R-loop formation. To grow, topA mutants acquire compensatory mutations, base substitutions in gyrA or gyrB (gyrase) or amplifications of a DNA region including parC and parE (topo (...) IV). topB mutants grow normally and topo III binds tightly to single-stranded DNA. What functions topo I and III share in vivo and how cells lacking these important enzymes can survive is unclear. Previously, a gyrB(Ts) compensatory mutation was used to construct topA topB null mutants. These mutants form very long filaments and accumulate diffuse DNA, phenotypes that appears to be related to replication from R-loops. Here, next generation sequencing and qPCR for marker frequency analysis were

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2018 PLoS genetics

72. Early Acute Microvascular Kidney Transplant Rejection in the Absence of Anti-HLA Antibodies Is Associated with Preformed IgG Antibodies against Diverse Glomerular Endothelial Cell Antigens. (PubMed)

Early Acute Microvascular Kidney Transplant Rejection in the Absence of Anti-HLA Antibodies Is Associated with Preformed IgG Antibodies against Diverse Glomerular Endothelial Cell Antigens. Although anti-HLA antibodies (Abs) cause most antibody-mediated rejections of renal allografts, non-anti-HLA Abs have also been postulated to contribute. A better understanding of such Abs in rejection is needed.We conducted a nationwide study to identify kidney transplant recipients without anti-HLA donor (...) inflammation and the presence of vasculitis (in 60.5%), interstitial hemorrhages (31.6%), or thrombotic microangiopathy (15.8%). Serum samples collected at the time of transplant showed that previously proposed anti-endothelial cell Abs-angiotensin type 1 receptor (AT1R), endothelin-1 type A and natural polyreactive Abs-did not increase significantly among patients with AMVR compared with a control group of stable kidney transplant recipients. However, 26% of the tested AMVR samples were positive for AT1R

2019 Journal of the American Society of Nephrology

73. Antibody engineering to generate SKY59, a long-acting anti-C5 recycling antibody. (PubMed)

Antibody engineering to generate SKY59, a long-acting anti-C5 recycling antibody. Modulating the complement system is a promising strategy in drug discovery for disorders with uncontrolled complement activation. Although some of these disorders can be effectively treated with an antibody that inhibits complement C5, the high plasma concentration of C5 requires a huge dosage and frequent intravenous administration. Moreover, a conventional anti-C5 antibody can cause C5 to accumulate in plasma (...) engineered anti-C5 antibody, SKY59, is expected to provide significant benefits for patients with complement-mediated disorders.

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2018 PLoS ONE

74. Non-HLA agonistic anti-angiotensin II type 1 receptor antibodies induce a distinctive phenotype of antibody-mediated rejection in kidney transplant recipients. (PubMed)

Non-HLA agonistic anti-angiotensin II type 1 receptor antibodies induce a distinctive phenotype of antibody-mediated rejection in kidney transplant recipients. Anti-angiotensin II type 1 receptor (AT1R) antibodies have been associated with allograft rejection. We hypothesized that circulating AT1R antibodies might identify kidney transplant recipients at increased risk of allograft rejection and loss who are not identified by the HLA system. We prospectively enrolled 1845 kidney transplant (...) recipients from two centers. Donor-specific HLA antibodies (DSAs) and AT1R antibodies were measured at the time of the first acute rejection episode or at 1 year post-transplant. Allograft biopsy was performed to evaluate the rejection phenotype and to assess for endothelial activation. Overall, 371 (20.1%) participants had AT1R antibodies, 334 (18.1%) had DSAs, and 133 (7.2%) had both. AT1R antibodies were associated with an increased risk of allograft loss (adjusted HR 1.49, 95% CI 1.07-2.06 for AT1R

2019 Kidney International

75. Early Antibody-Mediated Kidney Transplant Rejection Associated With Anti-Vimentin Antibodies: A Case Report. (PubMed)

Early Antibody-Mediated Kidney Transplant Rejection Associated With Anti-Vimentin Antibodies: A Case Report. Improving precision in predicting alloreactivity is an important unmet need and may require individualized consideration of non-HLA antibodies. We report a 21-year-old man with kidney failure from immunoglobulin A nephropathy who met all traditional criteria for a "low-risk" transplant for immune memory. He was unsensitized and received a haplotype-matched living donor kidney transplant (...) from his mother. There were no anti-HLA donor-specific antibodies and flow cross-match was negative. After immediate function, he developed delayed graft function on postoperative day 2. The transplant biopsy specimen was suggestive of antibody-mediated rejection and acute tubular injury with increased vimentin proximal tubular expression compared to the implantation biopsy specimen. He had a history of juvenile idiopathic arthritis, and non-HLA antibody screening demonstrated preformed anti

2019 American Journal of Kidney Diseases

76. Anti-mog (myelin oligodendrocyte glycoprotein) antibodies for the diagnosis of optic neuromyelitis and other demyelinating diseases

Anti-mog (myelin oligodendrocyte glycoprotein) antibodies for the diagnosis of optic neuromyelitis and other demyelinating diseases Anti-mog (myelin oligodendrocyte glycoprotein) antibodies for the diagnosis of optic neuromyelitis and other demyelinating diseases Anti-mog (myelin oligodendrocyte glycoprotein) antibodies for the diagnosis of optic neuromyelitis and other demyelinating diseases Oubiña M, Pichon-Riviere A, Augustovski F, García Martí S, Alcaraz A, Bardach A, Ciapponi A, López (...) A, Rey-Ares L Record Status This is a bibliographic record of a published health technology assessment from a member of INAHTA. No evaluation of the quality of this assessment has been made for the HTA database. Citation Oubiña M, Pichon-Riviere A, Augustovski F, García Martí S, Alcaraz A, Bardach A, Ciapponi A, López A, Rey-Ares L. Anti-mog (myelin oligodendrocyte glycoprotein) antibodies for the diagnosis of optic neuromyelitis and other demyelinating diseases. Buenos Aires: Institute for Clinical

2016 Health Technology Assessment (HTA) Database.

77. Quantitative and qualitative changes in anti-Neu5Gc antibody response following rabbit anti-thymocyte IgG induction in kidney allograft recipients. (PubMed)

Quantitative and qualitative changes in anti-Neu5Gc antibody response following rabbit anti-thymocyte IgG induction in kidney allograft recipients. Antibodies of non-human mammals are glycosylated with carbohydrate antigens, such as galactose-α-1-3-galactose (α-Gal) and N-glycolylneuraminic acid (Neu5Gc). These non-human carbohydrate antigens are highly immunogenic in humans due to loss-of-function mutations of the key genes involved in their synthesis. Such immunogenic carbohydrates (...) are expressed on therapeutic polyclonal rabbit anti-human T-cell IgGs (anti-thymocyte globulin; ATG), the most popular induction treatment in allograft recipients. To decipher the quantitative and qualitative response against these antigens in immunosuppressed patients, particularly against Neu5Gc, which may induce endothelial inflammation in both the graft and the host. We report a prospective study of the antibody response against α-Gal and Neu5Gc-containing glycans following rabbit ATG induction compared

2019 European journal of clinical investigation

78. Anti-nuclear antibody development is associated with poor treatment response to biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis. (PubMed)

Anti-nuclear antibody development is associated with poor treatment response to biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis. It has been well known that TNF-α inhibitor (TNFi) treatment for patients with rheumatoid arthritis (RA) is associated with anti-nuclear antibody (ANA) development. We previously reported that ANA development was associated with poor outcomes of infliximab (IFX) treatment (1). However, no replication studies have been reported (...) to date. In addition, whether the findings are true to general biological disease-modifying anti-rheumatic drugs (bDMARDs) is uncertain.To evaluate an association between treatment response and ANA development during bDMARDs treatment in RA and to analyze correlates of ANA development, Japanese RA patients treated with (n = 657) or without (n = 211) bDMARDs as a first line bDMARD were enrolled from a single center cohort. ANA was measured by an indirect immunofluorescence assay at multiple time points

2019 Seminars in arthritis and rheumatism

79. Anti-Fumarase Antibody as a Predictor of Functional Efficacy of Anti-VEGF Therapy for Diabetic Macular Edema. (PubMed)

Anti-Fumarase Antibody as a Predictor of Functional Efficacy of Anti-VEGF Therapy for Diabetic Macular Edema. To evaluate whether baseline titers of anti-fumarase antibody are associated with visual prognosis after anti-VEGF treatment for diabetic macular edema (DME).In this retrospective study, we investigated 52 eyes of 52 DME patients who received intravitreal injections of anti-VEGF drugs (ranibizumab or aflibercept) after blood sampling at baseline. Optical coherence tomography (OCT (...) ) images were obtained at every monthly visit. The serum titer of anti-fumarase antibody at baseline was measured using ELISA. We evaluated the relationship between the titer of anti-fumarase antibody at baseline and visual acuity (VA) improvement at 12 months.The serum titer of anti-fumarase IgG was related to the logMAR visual acuity (VA; R = 0.329, P = 0.017) and the disrupted ellipsoid zone (EZ; R = 0.364, P = 0.008) at baseline. The titer of this autoantibody was not associated with logMAR VA (R

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2019 Investigative Ophthalmology & Visual Science

80. Anti-plasminogen antibodies in ANCA-associated vasculitis: An optimized anti-plasminogen assay. (PubMed)

Anti-plasminogen antibodies in ANCA-associated vasculitis: An optimized anti-plasminogen assay. Anti-plasminogen antibodies (α-PLG) were previously detected in a subpopulation of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients, showing a relation to renal lesions and outcome. Several studies showed different proportions of α-PLG positive AAV patients, possibly due to differences in the assays used. We here present a new, optimized α-PLG Enzyme-Linked Immuno

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2018 PLoS ONE

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