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3. Developing a Molecular Classifier to Predict Graft Loss in Lung Transplant Transbronchial Biopsies

Author

Gauthier, P.T., primary, Mackova, M., additional, Hachem, R., additional, Havlin, J., additional, Hirji, A., additional, Jaksch, P., additional, Juvet, S., additional, Keshavjee, S., additional, Klepetko, W., additional, Kreisel, D., additional, Kubisa, B., additional, Levine, D.J., additional, Lischke, R., additional, Piotrowska, M., additional, Simonek, J., additional, Snell, G., additional, Timofte, I., additional, Weinkauf, J., additional, Westall, G., additional, Zajacova, A., additional, Halloran, K., additional, and Halloran, P., additional

Published
2024
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4. Genome-Wide Molecular Analysis of Heart Transplant Endomyocardial Biopsies Separately Analyzing Rejection and Parenchymal Injury

Author

Halloran, P.F., primary, Madill-Thomsen, K.S., additional, Mackova, M., additional, Aliabadi-Zuckermann, A.Z., additional, Cadeiras, M., additional, Crespo-Leiro, M., additional, Deng, M., additional, Goekler, J., additional, Hall, S., additional, Jamil, A., additional, Kim, D.H., additional, Kobashigawa, J., additional, MacDonald, P., additional, Patel, J., additional, Potena, L., additional, Shah, K., additional, Stehlik, J., additional, and Zuckermann, A., additional

Published
2024
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6. Developing a Molecular Classifier to Predict Graft Loss in Lung Transplant Mucosal Biopsies

Author

Gauthier, P.T., primary, Mackova, M., additional, Hachem, R., additional, Havlin, J., additional, Hirji, A., additional, Jaksch, P., additional, Juvet, S., additional, Keshavjee, S., additional, Klepetko, W., additional, Kreisel, D., additional, Kubisa, B., additional, Levine, D.J., additional, Lischke, R., additional, Piotrowska, M., additional, Simonek, J., additional, Snell, G., additional, Timofte, I., additional, Weinkauf, J., additional, Westall, G., additional, Zajacova, A., additional, Halloran, K., additional, and Halloran, P., additional

Published
2024
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7. Treatment Responses in Histologic Versus Molecular Diagnoses of Lung Rejection.

Author

Zajacova, A., Mackova, M., Halloran, K., Gauthier, P., Balko, J., Guney, M., Rakita, D., Svorcova, M., Kolarik, J., Vachtenheim Jr, J., Pozniak, J., Simonek, J., Fila, L., Lischke, R., Halloran, P. F., and Havlin, J.

Subjects
*GRAFT rejection, *LUNG transplantation, *MOLECULAR biology, *MOLECULAR diagnosis, *TRANSCRIPTOMES
Abstract

Histologic evaluation of allograft biopsies after lung transplantation has several limitations, suggesting that molecular assessment using tissue transcriptomics could improve biopsy interpretation. This single-center, retrospective cohort study evaluated discrepancies between the histology of transbronchial biopsies (TBBs) with no rejection (NR) and T-cell mediated rejection (TCMR) by molecular diagnosis. The accuracy of diagnosis was assessed based on response to treatment. 54 TBBs from Prague Lung Transplant Program obtained between December 2015 and January 2020 were included. Patients with acute cellular rejection (ACR) grade = 1 by histology received anti-rejection treatment. Response to therapy was defined as an increase in FEV1 of = 10% 4 weeks post-biopsy compared to the pre-biopsy value. Among the 54 analyzed TBBs, 25 (46%) were concordant with histology, while 29 (54%) showed discrepancies. ACR grade 0 was found in 12 TBBs (22%) and grade A1 = 1 in 42 TBBs (78%). Treatment response was present in 14% in the NR group and in 50% in the TCMR group (p = 0.024). Our findings suggest that low-grade acute cellular rejection is less likely to be associated with molecular TCMR, which might better identify lung transplant recipients who benefit from therapy. [ABSTRACT FROM AUTHOR]

Published
2024
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9. (1193) The Molecular Microscope Diagnostic System versus Histology in the Evaluation of Acute Cellular Rejection in Lung Transplant Recipients

Author

Zajacova, A., primary, Mackova, M., additional, Halloran, K., additional, Rakita, D., additional, Svorcova, M., additional, Vachtenheim, J., additional, Pozniak, J., additional, Simonek, J., additional, Fila, L., additional, Lischke, R., additional, Halloran, P.F., additional, and Havlin, J., additional

Published
2023
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11. Molecular states associated with dysfunction and graft loss in heart transplants.

Author

Halloran, PF, Madill-Thomsen, K, Mackova, M, Aliabadi-Zuckermann, AZ, Cadeiras, M, Crespo-Leiro, MG, Depasquale, EC, Deng, M, Gökler, J, Hall, SA, Kim, DH, Kobashigawa, J, Macdonald, P, Potena, L, Shah, K, Stehlik, J, Zuckermann, A, Reeve, J, Halloran, PF, Madill-Thomsen, K, Mackova, M, Aliabadi-Zuckermann, AZ, Cadeiras, M, Crespo-Leiro, MG, Depasquale, EC, Deng, M, Gökler, J, Hall, SA, Kim, DH, Kobashigawa, J, Macdonald, P, Potena, L, Shah, K, Stehlik, J, Zuckermann, A, and Reeve, J

Abstract

BACKGROUND: We explored the changes in gene expression correlating with dysfunction and graft failure in endomyocardial biopsies. METHODS: Genome-wide microarrays (19,462 genes) were used to define mRNA changes correlating with dysfunction (left ventricular ejection fraction [LVEF] ≤ 55) and risk of graft loss within 3 years postbiopsy. LVEF data was available for 1,013 biopsies and survival data for 779 patients (74 losses). Molecular classifiers were built for predicting dysfunction (LVEF ≤ 55) and postbiopsy 3-year survival. RESULTS: Dysfunction is correlated with dedifferentiation-decreased expression of normal heart transcripts, for example, solute carriers, along with increased expression of inflammation genes. Many genes with reduced expression in dysfunction were matrix genes such as fibulin 1 and decorin. Gene ontology (GO) categories suggested matrix remodeling and inflammation, not rejection. Genes associated with the risk of failure postbiopsy overlapped dysfunction genes but also included genes affecting microcirculation, for example, arginase 2, which reduces NO production, and endothelin 1. GO terms also reflected increased glycolysis and response to hypoxia, but decreased VEGF and angiogenesis pathways. T cell-mediated rejection was associated with reduced survival and antibody-mediated rejection with relatively good survival, but the main determinants of survival were features of parenchymal injury. Both dysfunction and graft loss were correlated with increased biopsy expression of BNP (gene NPPB). Survival probability classifiers divided hearts into risk quintiles, with actuarial 3-year postbiopsy survival >95% for the highest versus 50% for the lowest. CONCLUSIONS: Dysfunction in transplanted hearts reflects dedifferentiation, decreased matrix genes, injury, and inflammation. The risk of short-term loss includes these changes but is also associated with microcirculation abnormalities, glycolysis, and response to hypoxia.

Published
2023

14. The War in Ukraine and the Participation of St. Elizabeth University of Health and Social Work in Helping at Border Crossing Points

Author

Murgova, A., primary, Popovicova, M., additional, Krcmery, V., additional, Olah, M., additional, Jurasek, M., additional, Vansac, P., additional, Barkasi, D., additional, Gulasova, M., additional, Kenderesova, A., additional, Dancakova, M., additional, Tkacikova, Z., additional, Mackova, M., additional, Samudovska, G., additional, Jackulikova, M., additional, Sulcova, J., additional, Ivankova, V., additional, and Hudakova, T., additional

Published
2022
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15. Bioremediation of PCBs from Contaminated Soil

Author

Demnerová, K., Macková, M., Kučerová, P., Chromá, L., Nováková, H., Leigh, M. B., Burkhard, J., Pazlarová, J., Macek, T., Šašek, Václav, editor, Glaser, John A., editor, and Baveye, Philippe, editor

Published
2003
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16. PCB — Approaches to Removal From the Environment : Current Status of Bioremediation in the Czech Republic

Author

Demnerová, K., Macková, M., Pazlarová, J., Vosahlíková, M., Nováková, H., Jindrová, E., Ryslavá, E., Macek, T., Vrchotova, N., Brenner, V., Pavlů, L., Totevová, S., Kristoffer, T., Focht, D. D., Fava, F., Di Gioia, D., Marchetti, L., Fletcher, J. S., Leigh, M. B., Kucerová, P., Stiborová, H., Mateju, V., Sobotka, M., Kastanek, F., Kastanek, P., Kasák, L., Reible, Danny, editor, and Demnerova, Katerina, editor

Published
2002
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25. New Molecular Classification of Rejection in Heart Transplant Biopsies Reveals Relatively Little Three Year Graft Loss in Antibody-Mediated Rejection

Author

Halloran, PF, Madill-Thomsen, K, Mackova, M, Aliabadi-Zuckermann, A, Cadeiras, M, Crespo-Leiro, M, Depasquale, E, Deng, M, Goekler, J, Kim, DH, Kobashigawa, J, Parkes, M, Macdonald, P, Potena, L, Shah, K, Stehlik, J, Zuckermann, A, Halloran, PF, Madill-Thomsen, K, Mackova, M, Aliabadi-Zuckermann, A, Cadeiras, M, Crespo-Leiro, M, Depasquale, E, Deng, M, Goekler, J, Kim, DH, Kobashigawa, J, Parkes, M, Macdonald, P, Potena, L, Shah, K, Stehlik, J, and Zuckermann, A

Published
2021

28. New Molecular Classification of Rejection in Heart Transplant Biopsies Reveals Relatively Little Three Year Graft Loss in Antibody-Mediated Rejection

Author

Halloran, P.F., primary, Madill-Thomsen, K., additional, Mackova, M., additional, Aliabadi-Zuckermann, A., additional, Cadeiras, M., additional, Crespo-Leiro, M., additional, Depasquale, E., additional, Deng, M., additional, Goekler, J., additional, Kim, D.H., additional, Kobashigawa, J., additional, Parkes, M., additional, Macdonald, P., additional, Potena, L., additional, Shah, K., additional, Stehlik, J., additional, and Zuckermann, A., additional

Published
2021
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40. Beta-N-Acetylhexosaminidases accept 4-deoxy-N-acetylhexosaminides as substrates

Author

Slamova K., Bojarova P., Gazak R., Tramice A., Kulik N., Mackova M., and Kren V.

Abstract

b-N-Acetylhexosaminidases (EC 3.2.1.52, CAZy GH20) possess so called wobbling specificity, which means that they cleave substrates both in gluco- and galacto- configurations, with the activity ratio depending on the enzyme source. Here we present a new finding that fungal b-N-acetylhexosaminidases are also able to hydrolyze and transfer 4-deoxy-N-acetylhexosaminides. This fact clearly demonstrates that the 4-hydroxy moiety at the substrate pyranose is not essential for the binding of the substrate to the enzyme's active site, which was also confirmed by molecular docking of the tested compounds into the model of the active site of b-N-acetylhexosaminidase from Aspergillus oryzae. A set of four 4-deoxy-N-acetylhexosaminides was prepared via chemical synthesis and screened against a panel of b-N-acetylhexosaminidases from various types of sources (fungal, human, animal, plant and bacterial representatives) for hydrolysis. The results of this screening as well as structures of 4-deoxy disaccharides prepared by transglycosylation reaction using b-N-acetylhexosaminidase fromTalaromyces flavus are reported. This structure-function relationship study will be used in the design of new b-N-acetylhexosaminidase inhibitors and for the synthesis of novel type of glycomimetics.

Published
2009

41. Induction and characterization of an unusual alpha-D-galactosidase from Talaromyces flavus

Author

Simerska P., Monti D., Cechova I., Pelantova H., Mackova M., Bezouska K., Riva S., and Kren V.

Abstract

An extracellular alpha-D-galactosidase from Talaromyces flavus CCF 2686 with extremely broad and unusual acceptor specificity is produced exclusively in the presence of the specific inducer--6-deoxy-d-glucose (quinovose). The procedure for the preparation of this very expensive substance has been modified and optimized. Surprisingly, any of other common alpha-D-galactosidase inducers or substrates, e.g., d-galactose, melibiose and raffinose, did not stimulate its production. The crude alpha-D-galactosidase preparation was purified by anion-exchange chromatography and three isoenzymes with different substrate specificities were identified. The main isoenzyme ( alpha-Gal1) was further purified by cation-exchange chromatography and fully characterized. When compared with other alpha-galactosidases and also with other isoenzymes produced by T. flavus, it showed a markedly different regioselectivity and also negligible hydrolytic activity towards melibiose. Moreover, it was active on polymeric substrates (locust bean gum, guar gum) and significantly inhibited by alpha-D-galactopyranosyl azide, D-galactose, D-xylose, melibiose, methyl alpha- and beta-D-galactopyranoside and lactose.

Published
2007

42. Unique transglycosylation potential of extracellular alpha-D-galactosidase from Talaromyces flavus

Author

Simerska P., Kuzma M., Monti D., Riva S., Mackova M., and Kren V.

Abstract

The transglycosylation potential of the extracellular alpha-D-galactosidase from the filamentous fungus Talaromyces flavus CCF 2686, chosen as the best enzyme from the screening, was investigated using a series of sterically hindered alcohols (primary, secondary and tertiary) as galactosyl acceptors. Nine alkyl alpha-D-galactopyranosides derived from the following alcohols - tert-butyl alcohol, 2-methyl-2-butyl alcohol, 2-methyl-1-propyl alcohol, 2,2,2-trifluoroethyl alcohol, 2-propyn-1-ol, n-pentyl alcohol, 3,5-dihydroxybenzyl alcohol, 1-phenylethyl alcohol and 1,4-dithio-dl-threitol - were prepared on a semi-preparative scale. This demonstrates a broad synthetic potential of the T. flavus alpha-D-galactosidase that has not been observed with another enzyme tested. Moreover, this enzyme exhibits good transglycosylation yields (6-34%). The enzymatic synthesis of tert-butyl alpha-D-galactopyranoside by transglycosylation was studied in detail.

Published
2006

43. The Molecular Microscope Diagnostic System versus Histology in the Evaluation of Acute Cellular Rejection in Lung Transplant Recipients.

Author

Zajacova, A., Mackova, M., Halloran, K., Rakita, D., Svorcova, M., Vachtenheim, J., Pozniak, J., Simonek, J., Fila, L., Lischke, R., Halloran, P.F., and Havlin, J.

Subjects
*GRAFT rejection, *LUNG transplantation, *FORCED expiratory volume, *EXPIRATORY flow, *HISTOLOGY, *MICROSCOPES
Abstract

Histologic evaluation of allograft injury after lung transplantation has several limitations that may be aided by the Molecular Microscope Diagnostic System (MMDx). We aimed to describe discrepancies between samples with no rejection (NR) and T-cell mediated rejection (TCMR) by MMDx compared to the histology and to analyze the relationship to response to treatment. In this single-center cohort study, biopsy samples obtained from 43 lung transplant recipients (LTR) between December 2015 and January 2020 in Prague Lung Transplant Center were analyzed by both histology and MMDx. All samples with NR and TCMR by MMDx with available pre- and post-biopsy spirometry were included. Patients with histologically proven acute cellular rejection (ACR) grade ≥ 1 received antirejection treatment. Response to treatment was assessed in 4 weeks after the biopsy and defined as an increase in forced expiratory volume in 1 second (FEV1) ≥ 10% compared to FEV1 before biopsy. In total 54 samples were included (surveillance biopsies n=21, 38.9%; indication n=33, 61.1%). In 25 (46.3%) samples MMDx was concordant with the histological diagnosis and discrepancies were present in 29 samples (53.7%). ACR grade 0 was present in 12 (22.2%) and grade A1 ≥ 1 in 42 samples (77.8%). In the group with ACR grade A0, MMDx agreed in 11 samples (91.7%) and disagreed in 1 (8.3%). The group with ACR grade ≥ A1 showed NR by MMDx in 28 (66.7%) and TCMR in 14 samples (33.3%). Response to treatment was present in 4 LTRs in the NR group (14.3%) and 7 LTRs in the TCMR group (50.0%). Five of the non-responders in ACR ≥ A1 by histology and TCMR by MMDx had chronic lung allograft dysfunction present at the time of biopsy (71.4%) (Fig. 1). Our findings suggest that histology overestimates the diagnosis of acute cellular rejection and that MMDx offers additional insights in biopsies from lung transplant recipients. [ABSTRACT FROM AUTHOR]

Published
2023
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45. Correlation among the BRAF Gene Mutation Status, Clinicopathological Features of Primary Tumour, and Lymph Node Metastasizing of Papillary Thyroid Carcinoma

Author

Lukas, J., additional, Drabek, J., additional, Dudesek, B., additional, Vazan, P., additional, Stranska, J., additional, Jancik, S., additional, Mackova, M., additional, Syrucek, M., additional, Lukas, D., additional, Duskova, J., additional, Dundr, P., additional, Hintnausova, B., additional, and Jiskra, J., additional

Published
2014
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