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Öğe BENZIMIDAZOLE SCHIFF BASES MICROWAVE ASSISTED SYNTHESIS AND THE EFFECT ON LEUKEMIA CELLS WITH FLOW CYTOMETRY(Editura Acad Romane, 2019) Celik, Seyma Celikbilek; Vatansev, Husamettin; Koc, Ziya ErdemThe present paper introduces a simple and efficient method for the synthesis of a 2-aryl-substituted benzimidazole by heterocyclization of 1,2-phenylenediamine and 5-aminoisophthalic acid in the presence of polyphosphoric acid as catalyst under solvent-less conditions, which produced good yield of corresponding benzimidazoles in a short reaction time. Two new bisbenzimidazoles and tetrakisbenzimidazole Schiff bases were synthesized by reaction between 3,5-di(1H-benzo[d]imidazol-2-yl)aniline (BIMA) and terephthalaldehyde or 4-formylbenzoic acid. The condensations proceed in short time to give products which, in certain instances, are not readily attainable by conventional condensation techniques. Due to its good performance, the microwave device used in household was preferred. The structures of the compounds were assigned by FT-IR, H-1 NMR, C-13 NMR and elemental analysis. The effects of benzimidazoles and Schiff bases on the cancerous cells have been known. Synthesized by bisbenzimidazole and bisbenzimidazole/tetrakisbenzimidazole-Schiff bases derivatives 3,5-di(1H-benzo[d]imidazol-2-yl)aniline (BIMA), N, N'-(1,4-phenylenebis(methan-1-yl-1-ylidene))bis(3,5-di(1H-benzo[d]imidazol-2-yl)aniline) (PM-BIMA), (E)-4-((3,5-di(1H-benzo[d]imidazol-2-yl)phenylimino)methyl)benzoic acid (BIM-PMBA) with flow cytometric analysis was performed, blastic cells containing 90%. We measured rates of cell death in cells blast on the matter.Öğe Combined immunodeficiency caused by a loss-of-function mutation in DNA polymerase delta 1(Mosby-Elsevier, 2020) Cui, Ye; Keles, Sevgi; Charbonnier, Louis-Marie; Jule, Amelie M.; Henderson, Lauren; Celik, Seyma Celikbilek; Reisli, IsmailBackground: Mutations affecting DNA polymerases have been implicated in genomic instability and cancer development, but the mechanisms by which they can affect the immune system remain largely unexplored. Objective: We sought to establish the role of DNA polymerase M catalytic subunit (POLD1) as the cause of a primary immunodeficiency in an extended kindred. Methods: We performed whole-exome and targeted gene sequencing, lymphocyte characterization, molecular and functional analyses of the DNA polymerase delta (Pol delta) complex, and T- and B-cell antigen receptor repertoire analysis. Results: We identified a missense mutation (c. 3178C>T; p.R1060C) in POLD1 in 3 related subjects who presented with recurrent, especially herpetic, infections and T-cell lymphopenia with impaired T-cell but not B-cell proliferation. The mutation destabilizes the Pol delta complex, leading to ineffective recruitment of replication factor C to initiate DNA replication. Molecular dynamics simulation revealed that the R1060C mutation disrupts the intramolecular interaction between the POLD1 CysB motif and the catalytic domain and also between POLD1 and the Pol delta subunit POLD2. The patients exhibited decreased numbers of naive CD4 and especially CD8 T cells in favor of effector memory subpopulations. This skewing was associated with oligoclonality and restricted T-cell receptor beta-chain V-J pairing in CD8(+) but not CD4(+) T cells, suggesting that POLDR1060C differentially affects peripheral CD8(+) T-cell expansion and possibly thymic selection. Conclusion: These results identify gene defects in POLD1 as a novel cause of T-cell immunodeficiency.Öğe THE INFILTRATION OF T AND B LYMPHOCYTES AND NK CELLS IN KIDNEY BIOPSIES OF PATIENTS WITH FABRY DISESE UNDER ENZYME REPLACEMENT THERAPHY(Oxford Univ Press, 2020) Turkmen, Kultigin; Esen, Hasan; Karaselek, Mehmet Ali; Celik, Seyma Celikbilek; Baloglu, Ismail; Guner, Sukru; Reisli, Ismail[Abstract Not Availabe]Öğe Intrauterine detection of DCLRE1C (Artemis) mutation by restriction fragment length polymorphism(Wiley, 2019) Karaselek, Mehmet Ali; Kapakli, Hasan; Keles, Sevgi; Guner, Sukru Nail; Celik, Seyma Celikbilek; Kurar, Ercan; Reisli, Ismail[Abstract Not Availabe]