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Catherine Fenselau - One of the best experts on this subject based on the ideXlab platform.
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Primary structure of bovine Adenosine Deaminase
Journal of pharmaceutical and biomedical analysis, 1996Co-Authors: Michele Kelly, Martha M. Vestling, Constance M. Murphy, S. Hua, T. Sumpter, Catherine FenselauAbstract:Derivatized bovine Adenosine Deaminase is used in enzyme replacement therapy and as an adjunct to gene therapy against severe combined immunodeficiency syndrome. Although a gene sequence is known for human Adenosine Deaminase, the structure of the bovine enzyme has not been characterized. Structure studies using mass spectrometry are reported here that evaluate sequence, processing, post-translational modifications and the extent of homology between the human protein and its therapeutic surrogate.
Maria Grazia Roncarolo - One of the best experts on this subject based on the ideXlab platform.
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Gene therapy for Adenosine Deaminase deficiency.
Current opinion in allergy and clinical immunology, 2003Co-Authors: Alessandro Aiuti, Francesca Ficara, Federica Cattaneo, Claudio Bordignon, Maria Grazia RoncaroloAbstract:Purpose of review Gene therapy for severe combined immunodeficiency due to Adenosine Deaminase deficiency has moved from the early trials of safety and feasibility to recent studies demonstrating efficacy and clinical benefit. This review describes the latest advances in gene therapy trials for this condition using peripheral blood lymphocytes or hematopoietic progenitors. Recent findings In the first patients with severe combined immunodeficiency due to Adenosine Deaminase deficiency treated with peripheral blood lymphocytes, transduced T cells have been shown to persist for over 10 years, expressing transgenic Adenosine Deaminase, but the therapeutic effect of gene therapy remained difficult to assess because of the concomitant treatment with bovine Adenosine Deaminase conjugated to polyethylene-glycol (PEG-ADA). A recent report showed that discontinuation of PEG-ADA resulted in a strong selective advantage of gene corrected T cells associated with restoration of T cell functions and antibody responses to neoantigen, but incomplete correction of the metabolic defect. Follow-up studies in patients treated with engineered hematopoietic progenitors in the early trials revealed low marking levels of long-term living progenitors and limited clinical effect. Recently, an improved gene transfer protocol in bone marrow CD34+ cells combined with low-dose busulfan resulted in multilineage, stable engraftment of transduced progenitors at substantial levels, restoration of immune functions, correction of the Adenosine Deaminase metabolic defect, and proven clinical benefit, in the absence of PEG-ADA. Overall, no adverse effect or toxicity has been observed in patients treated with Adenosine Deaminase gene transfer in mature lymphocytes or hematopoietic progenitors. Summary Gene transfer in hematopoietic stem cells combined with nonmyeloablative conditioning is efficacious and might be extended to the treatment of other inherited and acquired disorders of the hematopoietic system.
Michele Kelly - One of the best experts on this subject based on the ideXlab platform.
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Primary structure of bovine Adenosine Deaminase
Journal of pharmaceutical and biomedical analysis, 1996Co-Authors: Michele Kelly, Martha M. Vestling, Constance M. Murphy, S. Hua, T. Sumpter, Catherine FenselauAbstract:Derivatized bovine Adenosine Deaminase is used in enzyme replacement therapy and as an adjunct to gene therapy against severe combined immunodeficiency syndrome. Although a gene sequence is known for human Adenosine Deaminase, the structure of the bovine enzyme has not been characterized. Structure studies using mass spectrometry are reported here that evaluate sequence, processing, post-translational modifications and the extent of homology between the human protein and its therapeutic surrogate.
S. S. Komsuoglu - One of the best experts on this subject based on the ideXlab platform.
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The diagnostic and prognostic value of Adenosine Deaminase in tuberculous pericarditis.
European heart journal, 1995Co-Authors: Baki Komsuoglu, Özhan Göldeli, Kaan Kulan, S. S. KomsuogluAbstract:Because of the difficulty in isolating the causative organism, pericardial tuberculosis is rarely diagnosed Adenosine Deaminase activity measured in the pericardial fluid of 108 patients was initially of undetermined origin. Subsequently, we classified five sources. (1) tuberculosis (20 cases); (2) idiopathy (82 cases); (3) neoplasia (three cases); (4) purulent bacterial infection (two cases), and (5) radiotherapy (one case). The highest mean Adenosine Deaminase value (126± 16·68 U. 1−1) was found in group 1; other values were 29·4 ±8·9, 27± 7·21, 29·5± 13·4, 26 U. 1−1 in the idiopathy, neoplasia, purulent bacterial infection and radiotherapy groups, respectively. There was a statistically significant difference between group I and the other groups ( P less than 0·001) indicating that the Adenosine Deaminase value has 100% sensitivity and 91% specificity. In addition, there was a positive correlation between high Adenosine Deaminase values and the development of constrictive pericarditis. In this study, two patients required pericardectomy. Therefore, the Adenosine Deaminase value is a significant prognostic indicator for the development of constrictive pericarditis in tuberculous pericarditis.
R W Light - One of the best experts on this subject based on the ideXlab platform.
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diagnostic value of Adenosine Deaminase in nontuberculous lymphocytic pleural effusions
European Respiratory Journal, 2003Co-Authors: Jimenez D Castro, Diaz G Nuevo, E Perezrodriguez, R W LightAbstract:Adenosine Deaminase (ADA) can aid in the diagnosis of tuberculous pleural effusions, but false-positive findings from lymphocytic effusions have been reported. The purpose of this study is to assess the ADA levels in nontuberculous lymphocytic pleural effusions (lymphocyte count >50%) of different aetiologies. Altogether, 410 nontuberculous lymphocytic pleural fluid samples were consecutively selected. These included malignant effusions (n=221), idiopathic effusions (n=76), parapneumonic effusions (n=35), postcoronary artery bypass graft surgery effusions (n=6), miscellaneous exudative effusions (n=21) and transudative effusions (n=51). The ADA level reached the diagnostic cut-off for tuberculosis (40 U·L−1) in seven of the 410 cases (1.71%). The negative predictive value of ADA for the diagnosis of pleural tuberculosis was 99% (403 of 407 cases) in the group of lymphocytic pleural effusions. In five of these seven patients ADA1 and ADA2 were measured, and in all these cases (100%) ADA1/ADAp correctly classified these lymphocytic effusions as nontuberculous (ratio <0.42). This prospective study provides additional evidence that Adenosine Deaminase levels in nontuberculous lymphocytic pleural effusions seldom exceed the cut-off set for tuberculous effusions. The pleural fluid Adenosine Deaminase levels were significantly higher in different types of exudative effusions than in transudates. An Adenosine Deaminase level <40 IU·L−1 virtually excluded a diagnosis of tuberculosis in lymphocytic pleural effusions. Adenosine Deaminase1/Adenosine Deaminasep correctly classified all nontuberculous lymphocytic pleural effusions with high Adenosine Deaminase levels.