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Your search keyword '"A. Girnita"' showing total 31 results
Start Over Author "A. Girnita" Publisher lippincott williams & wilkins
31 results on '"A. Girnita"'

30. A novel variant L263F in human inosine 5′-monophosphate dehydrogenase 2 is associated with diminished enzyme activity.

Author

Wang, Jian, Zeevi, Adriana, Webber, Steve, Girnita, Diana M., Addonizio, Linda, Selby, Rick, Hutchinson, Ian V., and Burckart, Gilbert J.

Abstract

Inosine 5′-monophosphate dehydrogenase 2 is required for purine synthesis in activated lymphocytes. Variants in the IMPDH2 gene may account for the large inter-individual variability in baseline enzyme activity, immunosuppressive efficacy and side effects in transplant recipients receiving mycophenolic acid. Therefore, the objective of this study was to identify and functionally characterize IMPDH2 variants.DNA samples from 152 solid organ transplant patients were screened at exons and exon/intron junctions of the IMPDH2 genes by PCR amplification followed by bidirectional direct DNA sequencing. Genetic variant was constructed by site-directed mutagenesis and transformed to an inosine 5′-monophosphate dehydrogenase-deficient strain of Escherichia coli h712. Proteins were purified to homogeneity and the enzymatic activity was measured by reduced nicotinamide adenine dinucleotide production.Nine genetic variants were identified in the IMPDH2 gene, with frequencies of the rarer alleles ranging from 0.5 to 10.2%. A novel nonsynonymous variant L263F was identified, and the kinetic assay demonstrated that the inosine 5′-monophosphate dehydrogenase activity of L263F variant was decreased to 10% of the wild-type. The Ki for mycophenolic acid inhibition of the L263F variant was comparable with the wild-type, and the variant Km for inosine 5′-monophosphate and nicotinamide adenine dinucleotide did not change significantly.IMPDH2 has low genetic diversity, but the nonsynonymous variant L263F has a significant impact on inosine 5′-monophosphate dehydrogenase activity. This novel functional variant may be one of the factors contributing to the inter-individual difference of baseline inosine 5′-monophosphate dehydrogenase activity as well as drug efficacy and adverse events in transplant patients. [ABSTRACT FROM AUTHOR]

Published
2007
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31. Reducing Donor-specific Antibody During Acute Rejection Diminishes Long-term Renal Allograft Loss: Comparison of Early and Late Rejection.

Author

Lichvar AB, Tremblay S, Leino AD, Shields AR, Cardi MA, Abu Jawdeh BG, Govil A, Kremer J, Cuffy M, Paterno F, Diwan T, Brailey P, Girnita A, Alloway RR, and Woodle ES

Subjects
Adult, Biomarkers blood, Bortezomib adverse effects, Down-Regulation, Female, Graft Rejection blood, Graft Rejection diagnosis, Graft Rejection immunology, Humans, Immunosuppressive Agents adverse effects, Male, Middle Aged, Phenotype, Proteasome Inhibitors adverse effects, Retrospective Studies, Time Factors, Treatment Outcome, Bortezomib therapeutic use, Graft Rejection therapy, Graft Survival drug effects, Immunosuppressive Agents therapeutic use, Isoantibodies blood, Kidney Transplantation adverse effects, Plasmapheresis adverse effects, Proteasome Inhibitors therapeutic use
Abstract

Background: Reduction in donor-specific antibody (DSA) has been associated with improved renal allograft survival after antibody-mediated rejection (AMR). These observations have not been separately analyzed for early and late AMR and mixed acute rejection (MAR). The purpose of this study was to evaluate long-term responses to proteasome inhibitor-based therapy for 4 rejection phenotypes and to determine factors that predict allograft survival., Methods: Retrospective cohort study evaluating renal transplant recipients with first AMR episodes treated with proteasome inhibitor-based therapy from January 2005 to July 2015., Results: A total of 108 patients were included in the analysis. Immunodominant DSA reduction at 14 days differed significantly (early AMR 79.6%, early MAR 54.7%, late AMR 23.4%, late MAR 21.1%, P < 0.001). Death-censored graft survival (DCGS) differed at 3 years postrejection (early AMR 88.3% versus early MAR 77.8% versus late AMR 56.7% versus late MAR 54.9%, P = 0.02). Multivariate analysis revealed that immunodominant DSA reduction > 50% at 14 days was associated with improved DCGS (odds ratio, 0.12, 95% CI, 0.02-0.52, P = 0.01)., Conclusions: In summary, significant differences exist across rejection phenotypes with respect to histological and DSA responses. The data suggest that DSA reduction may be associated with improved DCGS in both early and late AMR.

Published
2020
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