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Anti-Topoisomerase I Antibody

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81201. A phase I trial of humanized anti-interleukin 2 receptor antibody in renal transplantation. (PubMed)

A phase I trial of humanized anti-interleukin 2 receptor antibody in renal transplantation. The efficacy of murine monoclonal anti-interleukin 2 alpha chain receptor (Tac) antibodies is limited by a short half-life and the development of antibodies to the heterologous protein. The safety, pharmacokinetics-dynamics, and immunosuppressive effect of a humanized anti-Tac antibody (HAT) was evaluated in 12 renal transplant recipients. Ten patients received living related transplants (three HLA (...) subsequent side effects. None of the patients experienced opportunistic infections or malignancies. One patient developed low-titer anti-HAT antibodies, although the patient maintained high serum HAT concentrations throughout the study. Immune monitoring showed that there were no changes in the percentage or absolute counts of CD3 cells or T-cell subsets after HAT therapy. However, there was a significant decrease in the number of circulating lymphocytes that expressed free Tac. The overall harmonic mean

1997 Transplantation.

81202. Prevention of acute rejection episodes with an anti-interleukin 2 receptor monoclonal antibody. I. Results after combined pancreas and kidney transplantation. (PubMed)

Prevention of acute rejection episodes with an anti-interleukin 2 receptor monoclonal antibody. I. Results after combined pancreas and kidney transplantation. A prospective, randomized trial was conducted to evaluate the short-term and long-term effects of induction immunosuppression with the rat IgG 2a monoclonal antibody 33B3.1, directed against the human alpha chain of the interleukin 2-receptor, following primary, cadaveric, combined pancreas and kidney transplantation. Forty patients were (...) that, although a significantly higher rejection episode incidence was observed in patients treated with 33B3.1 monoclonal antibody as compared with ATG, similar long-term results can be obtained following primary cadaveric combined pancreas/kidney transplantation.

1994 Transplantation.

81203. Idiotypic vaccination with a murine anti-dsDNA antibody: phase I study in patients with nonactive systemic lupus erythematosus with nephritis. (PubMed)

Idiotypic vaccination with a murine anti-dsDNA antibody: phase I study in patients with nonactive systemic lupus erythematosus with nephritis. To determine the safety and immunogenicity of an idiotypic anti-dsDNA vaccine in patients with nonactive systemic lupus erythematosus (SLE) and stable lupus nephritis.Patients with SLE with a history of nephritis were randomized for vaccination with the murine anti-dsDNA monoclonal antibody (Mab) 3E10 in a dose ranging, double blind, placebo controlled (...) study (phase I).Of the 9 patients injected with Mab 3E10, 5 showed a human anti-mouse antibody (HAMA) response, in large part antiidiotypic, which developed within the first 3 months in 3 strong HAMA responders, and more than one year after immunization in an initially weak HAMA responder. All but one nonresponder were receiving low dose prednisone. No adverse events, in particular no evidence of lupus flares, and no untoward laboratory findings were reported over a followup of 2 years.In patients

1999 The Journal of rheumatology

81204. Induction of anti-progesterone immunity and pregnancy blocking by anti-progesterone anti-idiotypes. Variable efficacy of polyclonal Ab2 antibodies directed against a panel of closely related Ab1 antibodies. (PubMed)

Induction of anti-progesterone immunity and pregnancy blocking by anti-progesterone anti-idiotypes. Variable efficacy of polyclonal Ab2 antibodies directed against a panel of closely related Ab1 antibodies. Polyclonal rabbit anti-idiotypes (Ab2) have been raised against three mouse monoclonal antiprogesterone Ab1 antibodies (DB3, 11/32, 11/64) closely related in VH and VL sequences. The anti-idiotypes were characterized for specificity and used to immunize groups of female mice. The latter (...) responded with production of anti-progesterone (Ab3) antibodies, confirming the ability of anti-idiotypes to mimic the immunogenicity of a steroid. The response to one of the anti-idiotypic reagents (anti-DB3-id) was 5-10 times stronger than those to the others, despite close sequence homology between the idiotypes. Moreover, immunization with anti-DB3-id led to a reduction in fertility rate from 90% (control) to 30%, whereas immunization with the other anti-idiotypes was without effect. Sequence

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1991 Immunology

81205. Relation between lymphocytotoxic antibodies, anti-DNA antibodies and a common anti-DNA antibody idiotype PR4 in patients with systemic lupus erythematosus, their relatives and spouses. (PubMed)

Relation between lymphocytotoxic antibodies, anti-DNA antibodies and a common anti-DNA antibody idiotype PR4 in patients with systemic lupus erythematosus, their relatives and spouses. Forty-two patients with systemic lupus erythematosus (SLE), 65 of their healthy relatives and 20 spouses were studied for the presence of lymphocytotoxic antibodies (LCA), anti-lymphocyte antibodies (ALA), antibodies to DNA and a common idiotype (Id) PR4. Seventy-one per cent of the patients had positive levels (...) of LCA, and in 34% the PR4 Id was detected; normal levels were found in their families. Anti-PR4, an anti-Id, failed to block the lymphocytotoxic activity in those nine patients who both carried the Id and had LCA. This indicates that the Id was not present on LCA. There was no correlation between anti-DNA antibodies and LCA, suggesting that different mechanisms are involved in their expression.

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1989 Clinical and experimental immunology

81206. Diversity of anti-HLA-DR antibodies elicited by distinct anti-idiotypic monoclonal antibodies recognizing idiotopes co-expressed by the immunizing monoclonal antibody. (PubMed)

Diversity of anti-HLA-DR antibodies elicited by distinct anti-idiotypic monoclonal antibodies recognizing idiotopes co-expressed by the immunizing monoclonal antibody. Analysis at the clonal level of the idiotypic network has identified differences in fine specificity between antigen-binding anti-anti-idiotypic (anti-anti-id) monoclonal antibody (mAb) and the original mAb as well as among antigen-binding anti-anti-idiotypic (anti-id) mAb. However, the diversity of humoral immune responses (...) elicited by anti-id mAb recognizing idiotopes co-expressed on the immunizing mAb has not been analysed. Since this information may contribute to our understanding of the role of anti-id antibodies in the generation of diversity in the course of an immune response, we have compared the fine specificity and idiotype profile of two subsets of anti-HLA-DR mAb generated with the anti-id mAb F5-444 and F5-830. The latter mAb recognize idiotopes co-expressed in the antigen-combining site of the immunizing

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1992 Immunology

81207. P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities (PubMed)

P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities Human CD3-16+56+ natural killer (NK) cells have been shown to display a clonally distributed ability to recognize major histocompatibility complex (MHC) class I alleles. Opposite to T lymphocytes, in NK cells, specific recognition of MHC class I (...) , its F(ab')2 fragment and the XA141 mAb reconstituted the lysis of C1R, a Fc gamma R- target cell expressing Cw4 as the only serologically detected class I antigen. Thus, it appears that masking of different members of p58 molecules prevents recognition of "protective" MHC class I alleles and thus the delivering of inhibitory signals. Further support to the concept that p58 molecules represent a NK receptor delivering a negative signal was provided by experiments in which the entire anti-p58 mAbs

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1993 The Journal of experimental medicine

81208. Electron microscopy of the reactions of anti-poly A. poly U and anti-poly I. poly C antibodies with synthetic polynucleotide complexes and natural nucleic acids. (PubMed)

Electron microscopy of the reactions of anti-poly A. poly U and anti-poly I. poly C antibodies with synthetic polynucleotide complexes and natural nucleic acids. The reactions between purified anti-poly A. poly U and-poly I. poly C. antibodies (IgG and IgM), and synthetic and natural polynucleotides were visualized at the molecular level. This was achieved by the use of fine tungsten bidirectional shadowing of molecules adsorbed onto thin carbon films, combined with dark field electron (...) microscopic observation. A progression was observed from monogamous multivalency (binding of a single multifunctional antigen molecule with several combining sites of the same antibody molecule simultaneously) (Crothers and Metzger, 1972, Immunochemistry, 9, 341-357), to aggregation. Different types of figures were observed, among which loops formed by the coiling of the antigen around a single IgM molecule were very frequently seen. The tendency of IgG antibodies to bind cooperatively to certain antigens

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1980 Nucleic acids research

81209. Anti-idiotypes to anti-Lolp I (Rye) antibodies in allergic and non-allergic individuals. Influence of immunotherapy. (PubMed)

Anti-idiotypes to anti-Lolp I (Rye) antibodies in allergic and non-allergic individuals. Influence of immunotherapy. Anti-idiotypes (aId) reacting with anti-Lol I (Lolp I; Rye I) antibodies were detected by their ability to bind to radioiodinated F(ab')2 anti-Lol I. Sera were tested after removal of anti-Lol I and anti-heavy and light chain activity by adsorption on Lol I-Sepharose 4B and normal human serum Sepharose 4B. The binding of aId to Id was inhibited by affinity purified anti-Lol I (...) relationship between changes in serum levels of aId and of IgG or IgE anti-Lol I. Most interestingly, aId were also detected in non-allergic individuals; in this case, the levels of aId were not influenced by the pollen season. The data suggest that Id-aId interactions may play a role in the regulation of anti-Lol I antibody production.

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1986 Clinical and experimental immunology

81210. In-vivo modulation of thymus-derived lymphocytes with monoclonal antibodies in mice. I. Effect of anti-Thy-1 antibody on the tissue distribution of lymphocytes. (PubMed)

In-vivo modulation of thymus-derived lymphocytes with monoclonal antibodies in mice. I. Effect of anti-Thy-1 antibody on the tissue distribution of lymphocytes. A procedure is described for the in vivo removal of all detectable T lymphocytes from spleen and lymph nodes in mice. A single intraperitoneal injection of monoclonal anti-Thy-1 antibody into mice leads to rapid depletion of functional T cells from peripheral lymphoid organs, but not thymus. The extent of T-cell depletion is dependent (...) on the cytotoxic titre of the anti-Thy-1 antibody used. Antibody with a median cytotoxic titre greater than 10(6) causes the complete removal of cells bearing Thy-1, Lyt-1 and Lyt-2 surface antigens from peripheral lymphoid populations in 3 days. Eight days after treatment Thy-1+, Lyt-1+ and Lyt-2+ cells begin to reappear in these organs. Splenic B cells, assayed by the expression of surface immunoglobulin (sIg) and by mitogenic responsiveness to bacterial lipopolysaccharide (LPS), are not affected

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1983 Immunology

81211. Association between maternal antibodies to the external envelope glycoprotein and vertical transmission of human T-lymphotropic virus type I. Maternal anti-env antibodies correlate with protection in non-breast-fed children. (PubMed)

Association between maternal antibodies to the external envelope glycoprotein and vertical transmission of human T-lymphotropic virus type I. Maternal anti-env antibodies correlate with protection in non-breast-fed children. Vertical transmission of human T-lymphotropic virus type I (HTLV-I) depends primarily on breast-feeding; substitution of bottle-feeding has reduced the transmission rate from 20% in breast-fed children to 3% among bottle-fed. To determine the correlates of transmission (...) were significantly higher than those among T-mothers (80 and 113, respectively) (P < 0.01). These data confirm that high-titered anti-HTLV-I antibodies in the long-feeding group correlate with milk-borne transmission of HTLV-I and, more importantly, imply that maternal anti-env antibodies may reduce the risk of non-milkborne infection.

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1995 Journal of Clinical Investigation

81212. Pathogenic role of anti-beta 2-glycoprotein I antibodies in antiphospholipid associated fetal loss: characterisation of beta 2-glycoprotein I binding to trophoblast cells and functional effects of anti-beta 2-glycoprotein I antibodies in vitro. (PubMed)

Pathogenic role of anti-beta 2-glycoprotein I antibodies in antiphospholipid associated fetal loss: characterisation of beta 2-glycoprotein I binding to trophoblast cells and functional effects of anti-beta 2-glycoprotein I antibodies in vitro. Antiphospholipid antibodies reacting with beta2-glycoprotein I (beta 2GPI) have been associated with recurrent fetal loss and pregnancy complications.To investigate whether specific mutations in the phospholipid binding site of beta 2GPI might affect its (...) binding to trophoblast and in turn the anti-beta 2GPI antibody induced functional effects.beta 2GPI adhesion to trophoblast was evaluated as human monoclonal IgM or polyclonal IgG anti-beta 2GPI antibody binding to trophoblast monolayers cultured (1) in complete medium; (2) in serum-free medium; (3) after serum starvation in the presence of purified human beta 2GPI; or (4) in the presence of beta 2GPI with single or multiple mutations in the amino acid loop Cys(281)-Lys-Asn-Lys-Glu-Lys-Lys-Cys(288

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2005 Annals of the Rheumatic Diseases

81213. Expression of immunoglobulin-cross-reactive molecules by neoplastic human T cells. I. Surface detection and isolation of molecules reactive with chicken anti-F(ab')2, anti-alpha and anti-mu antibodies. (PubMed)

Expression of immunoglobulin-cross-reactive molecules by neoplastic human T cells. I. Surface detection and isolation of molecules reactive with chicken anti-F(ab')2, anti-alpha and anti-mu antibodies. There is evidence that the T-cell antigen receptor is immunoglobulin-related and that normal human T cells express surface determinants which cross-react with chicken anti-F(ab')2, anti-alpha and anti-mu antibodies. Surface marker study of six neoplastic human T cell lines suggested that F(ab')2 (...) ')2-CRMs identified major components of mol. wt. 135,000 and mol. wt. 330,000 respectively. Immunoprecipitation of 125I-labelled F(ab')2-CRMs by chicken anti-F(ab')2 followed by SDS-PAGE under reducing conditions identified major components of mol. wt. 80,000 and mol. wt. of 51,000 from CCRF-CEM-derived F(ab')2-CRMs and tentatively identified components of mol. wt. 52,000 and mol. wt. 23,000 from MOLT-4-derived F(ab')2-CRMs.

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1983 Immunology

81214. Induction of an anti-Fab, anti-DNA and anti-RNA polymerase I autoantibody response network in rabbits immunized with SLE anti-DNA antibody. (PubMed)

Induction of an anti-Fab, anti-DNA and anti-RNA polymerase I autoantibody response network in rabbits immunized with SLE anti-DNA antibody. Systemic lupus erythematosus (SLE)-like anti-IgG Fab autoantibodies (autoAb) were induced in rabbits by immunization with either human, mouse or rabbit anti-DNA Ab. In direct-binding radioimmunoassay (RIA), affinity-purified anti-normal rabbit (NR) Fab autoAb cross-reacted with normal mouse (NM) Fab, ssDNA (but not dsDNA), poly(dA,dT), and RNA polymerase I (...) (RPI). Affinity-purified anti-NM IgG Ab isolated from the same antisera cross-reacted with NR Fab, ssDNA and RPI. In inhibition RIA, soluble NR Fab inhibited anti-NR Fab binding to NR Fab and ssDNA, but enhanced binding to RPI. In contrast, ssDNA or RPI inhibitors had no effect upon autoAb binding to NR Fab. Anti-DNA, anti-RPI and anti-RPI 190 kD subunit autoAb, induced by immunization with lupus mouse anti-DNA Ab, also reacted with NM Fab, but were idiotypically specific for lupus mouse anti-DNA

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1993 Clinical and experimental immunology

81215. Chromosome studies in systemic sclerosis with consideration of antibodies to topoisomerase I. (PubMed)

Chromosome studies in systemic sclerosis with consideration of antibodies to topoisomerase I. Chromosome studies were performed on 11 patients with systemic sclerosis and on 35 control subjects. Nine patients with systemic sclerosis were positive for antibodies to topoisomerase I and two were negative. Of the 1100 metaphases from these 11 patients, 171 (15.5%) had chromosome breaks, compared with 61 of 3500 (1.7%) metaphases from normal control subjects. There were no statistically significant (...) differences in the numbers of chromosome breaks between men and women. The most common fragile site in patients with systemic sclerosis was at 3p14. The karyotype of all patients was normal. Chromosome breaks did not correlate with the presence of antibodies to topoisomerase I.

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1992 Annals of the Rheumatic Diseases

81216. DNA topoisomerase I binding to fibroblasts induces monocyte adhesion and activation in the presence of anti-topoisomerase I autoantibodies from systemic sclerosis patients. (PubMed)

DNA topoisomerase I binding to fibroblasts induces monocyte adhesion and activation in the presence of anti-topoisomerase I autoantibodies from systemic sclerosis patients. Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis due to excessive and dysregulated collagen production by fibroblasts. Previously, we reported that anti-DNA topoisomerase I (anti-topo I) antibodies bound specifically to fibroblast surfaces; however, we had not identified their antigenic target. We (...) undertook this study to characterize the target of anti-topo I antibodies on fibroblasts and the effects of their binding.Purified topo I or topo I released from apoptotic cells was tested for surface binding to a number of human cell types by cell-based enzyme-linked immunosorbent assay, flow cytometry, and indirect immunofluorescence. Antibodies purified from SSc patient and normal control sera were used to detect topo I binding. The consequences of topo I and anti-topo I binding to fibroblasts were

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2006 Arthritis and Rheumatism

81217. Correlation of serum anti-DNA topoisomerase I antibody levels with disease severity and activity in systemic sclerosis. (PubMed)

Correlation of serum anti-DNA topoisomerase I antibody levels with disease severity and activity in systemic sclerosis. To investigate correlations between serum levels of topoisomerase I-specific antibody (anti-topo I) and clinical features of systemic sclerosis (SSc), including disease severity (the total skin score [TSS]) and disease activity.Using highly sensitive enzyme-linked immunosorbent assays, we measured the levels of anti-topo I antibody, including total IgG, individual IgG (...) subclasses, and IgA, and analyzed their correlations with the TSS in 59 patients with SSc, all of whom had diffuse cutaneous involvement. Serial serum samples were obtained from 11 of these patients.The titers of anti-topo I antibody, including IgG and IgA, were positively correlated with the TSS, a measure of SSc disease severity. In 8 of the 11 patients from whom serial serum samples were obtained, changes in the levels of both IgG and IgA, when detectable, paralleled changes in the TSS. In 3 patients

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2003 Arthritis and Rheumatism

81218. Association of the PTPN22 R620W polymorphism with anti-topoisomerase I- and anticentromere antibody-positive systemic sclerosis. (PubMed)

Association of the PTPN22 R620W polymorphism with anti-topoisomerase I- and anticentromere antibody-positive systemic sclerosis. To determine any associations of the PTPN22 R620W single-nucleotide polymorphism (SNP) with systemic sclerosis (SSc) or with anticentromere antibody (ACA)-positive or anti-topoisomerase I (anti-topo I) antibody-positive SSc, in a case-control study of US white, black, Hispanic, and Choctaw Indian individuals.A total of 850 white, 130 black, 120 Hispanic, and 20 (...) Choctaw Indian patients with SSc were compared with 430 white, 164 black, 146 Hispanic, and 76 Choctaw Indian control subjects, respectively. All subjects were living in the US. PTPN22 SNP (rs2476601) genotyping was performed by TaqMan 5' allelic discrimination assay and pyrosequencing.The PTPN22 CT/TT genotype showed significant association with anti-topo I antibody-positive SSc in white patients (odds ratio [OR] 2.21, 95% confidence interval [95% CI] 1.3-3.7) and with ACA-positive white patients

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2006 Arthritis and Rheumatism

81219. Characterization of anti-idiotypic antibodies and their use as probes for determination of shared idiotopes expressed on murine and human IgE anti-rye I antibodies. (PubMed)

Characterization of anti-idiotypic antibodies and their use as probes for determination of shared idiotopes expressed on murine and human IgE anti-rye I antibodies. This study describes the production and characterization of rabbit anti-idiotypic antibodies (anti-ID Abs) against three idiotypes of three mAbs with different specificities. The anti-ID Abs were rendered idiotype specific by appropriate adsorption. Binding of labelled mAb to homologous anti-ID Ab bound to a polystyrene matrix (...) was completely inhibited when the same mAb was added. In contrast, addition of other mAbs sharing the same isotype and the same light chain but with different specificity did not affect the binding reaction. Each anti-ID Ab inhibited completely and selectively the reaction between the allergen and the homologous mAb idiotype. Labelled rye I binding to a given polystyrene-bound mAb idiotype was completely blocked if the relevant anti-ID Ab was used as an inhibitor. Murine polyclonal anti-rye I antisera

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1988 Immunology

81220. Clinical subsets, skin thickness progression rate, and serum antibody levels in systemic sclerosis patients with anti-topoisomerase I antibody. (PubMed)

Clinical subsets, skin thickness progression rate, and serum antibody levels in systemic sclerosis patients with anti-topoisomerase I antibody. To describe the clinical and laboratory features and natural history of the disease in systemic sclerosis (SSc; scleroderma) patients with anti-topoisomerase I (anti-topo I) antibody who have different skin thickness progression rates (STPRs).SSc patients (n = 212) who were anti-topo I antibody positive were divided into 5 subgroups based on STPRs. Skin (...) thickness was measured using the modified Rodnan skin thickness score (MRSS). Anti-topo I IgG antibody levels were determined.Sixty patients who were anti-topo I antibody positive had diffuse cutaneous SSc (dcSSc) with rapid progression, 82 had dcSSC with intermediate progression, and 29 had dcSSc with slow progression, 14 had limited cutaneous SSc (lcSSc) that became dcSSc, and 27 had lcSSc that did not change throughout. Patients beginning with lcSSc were younger at disease onset and had longer

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2007 Arthritis and Rheumatism

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