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Ankush Sachdeva, Biswajit Paul
Dobutamine stress echocardiography (DSE) has come a long way as establishing itself as a feasible, safe, effective, relatively cheaper non-invasive technique to detect population suffering from coronary artery disease (CAD) and following up patients post revascuralization. Besides these DSE is commonly used to diagnose low gradient, low flow true severe aortic stenosis (AS); differentiating it from pseudo- AS and to follow up patients with dilated cardiomyopathy (DCMP). Various non-invasive techniques have different sensitivity and specificity to accurately judge a viable myocardium and to accurately detect the improvement in regional wall motion abnormality (RWMA) post-revascularization, leading to an overall increase in left ventricular ejection fraction (LVEF)...
February 2016: Journal of the Association of Physicians of India
Harsh Kumar Garg
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Rajendra Prasad, Vladimir Poltoratsky, Esther W Hou, Samuel H Wilson
Rev1 is a member of the Y-family of DNA polymerases and is known for its deoxycytidyl transferase activity that incorporates dCMP into DNA and its ability to function as a scaffold factor for other Y-family polymerases in translesion bypass events. Rev1 also is involved in mutagenic processes during somatic hypermutation of immunoglobulin genes. In light of the mutation pattern consistent with dCMP insertion observed earlier in mouse fibroblast cells treated with a base excision repair-inducing agent, we questioned whether Rev1 could also be involved in base excision repair (BER)...
September 28, 2016: Nucleic Acids Research
Akira Sassa, Melike Ҫağlayan, Yesenia Rodriguez, William A Beard, Samuel H Wilson, Takehiko Nohmi, Masamitsu Honma, Manabu Yasui
Numerous ribonucleotides are incorporated into the genome during DNA replication. Oxidized ribonucleotides can also be erroneously incorporated into DNA. Embedded ribonucleotides destabilize the structure of DNA and retard DNA synthesis by DNA polymerases (pols), leading to genomic instability. Mammalian cells possess translesion DNA synthesis (TLS) pols that bypass DNA damage. The mechanism of TLS and repair of oxidized ribonucleotides remains to be elucidated. To address this, we analyzed the miscoding properties of the ribonucleotides riboguanosine (rG) and 7,8-dihydro-8-oxo-riboguanosine (8-oxo-rG) during TLS catalyzed by the human TLS pols κ and η in vitro...
September 22, 2016: Journal of Biological Chemistry
Nicole L Williams, Pengcheng Wang, Yinsheng Wang
DNA alkylation represents a major type of DNA damage and is generally unavoidable due to ubiquitous exposure to various exogenous and endogenous sources of alkylating agents. Among the alkylated DNA lesions, O(2)-alkylthymidines (O(2)-alkyldT) are known to be persistent and poorly repaired in mammalian systems and have been shown to accumulate in the esophagus, lung, and liver tissue of rats treated with tobacco-specific N-nitrosamines, i.e., 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN)...
October 17, 2016: Chemical Research in Toxicology
Josef Finsterer, Claudia Stöllberger
Objectives. Psychosis and left ventricular hypertrabeculation (or noncompaction) (LVHT) have not been described in the same patient. Here we report a patient with a long-term history of schizophrenia who was later diagnosed with dilated cardiomyopathy (dCMP) and LVHT. Case Report. A 47-year-old Caucasian male developed nondifferentiated schizophrenia at the age of 26 y. Since the age of 33 y he was regularly drinking alcohol. At the age of 47 y he developed heart failure. Transthoracic echocardiography showed an enlarged left ventricle, reduced systolic function, and surprisingly LVHT in the apical segment...
2016: Case Reports in Cardiology
Yu Jung Choi, Jun Ho Jang, So Hyun Park, Jin-Hee Oh, Dae Kyun Koh
Graves disease (GD) can lead to complications such as cardiac arrhythmia and heart failure. Although dilated cardiomyopathy (DCMP) has been occasionally reported in adults with GD, it is rare in children. We present the case of a 32-month-old boy with DCMP due to GD. He presented with irritability, vomiting, and diarrhea. He also had a history of weight loss over the past few months. On physical examination, he had tachycardia without fever, a mild diffuse goiter, and hepatomegaly. The chest radiograph showed cardiomegaly with pulmonary edema, while the echocardiography revealed a dilated left ventricle with an ejection fraction (EF) of 28%...
June 2016: Annals of Pediatric Endocrinology & Metabolism
Michael H Räz, Hannah R Dexter, Christopher L Millington, Barbara van Loon, David M Williams, Shana J Sturla
The generation of chemical alkylating agents from nitrosation of glycine and bile acid conjugates in the gastrointestinal tract is hypothesized to initiate carcinogenesis. O(6)-carboxymethylguanine (O(6)-CMG) is a product of DNA alkylation derived from nitrosated glycine. Although the tendency of the structurally related adduct O(6)-methylguanine to code for the misincoporation of TTP during DNA replication is well-established, the impact of the presence of the O(6)-CMG adduct in a DNA template on the efficiency and fidelity of translesion DNA synthesis (TLS) by human DNA polymerases (Pols) has hitherto not been described...
September 19, 2016: Chemical Research in Toxicology
Yanhua Li, Zhen Guo, Li Jin, Deqiang Wang, Zengqiang Gao, Xiaodong Su, Haifeng Hou, Yuhui Dong
In cells, dUMP is the intermediate precursor of dTTP in its synthesis during deoxynucleotide metabolism. In Gram-positive bacteria and eukaryotes, zinc-dependent deoxycytidylate deaminases (dCDs) catalyze the conversion of dCMP to dUMP. The activity of dCD is allosterically activated by dCTP and inhibited by dTTP. Here, the crystal structure of Streptococcus mutans dCD (SmdCD) complexed with dTTP is presented at 2.35 Å resolution, thereby solving the first pair of activator-bound and inhibitor-bound structures from the same species to provide a more definitive description of the allosteric mechanism...
July 2016: Acta Crystallographica. Section D, Structural Biology
Cristina E Requena, Guiomar Pérez-Moreno, András Horváth, Beáta G Vértessy, Luis M Ruiz-Pérez, Dolores González-Pacanowska, Antonio E Vidal
Decitabine (5-aza-2'-deoxycytidine, aza-dCyd) is an anti-cancer drug used clinically for the treatment of myelodysplastic syndromes and acute myeloid leukaemia that can act as a DNA-demethylating or genotoxic agent in a dose-dependent manner. On the other hand, DCTPP1 (dCTP pyrophosphatase 1) and dUTPase are two 'house-cleaning' nucleotidohydrolases involved in the elimination of non-canonical nucleotides. In the present study, we show that exposure of HeLa cells to decitabine up-regulates the expression of several pyrimidine metabolic enzymes including DCTPP1, dUTPase, dCMP deaminase and thymidylate synthase, thus suggesting their contribution to the cellular response to this anti-cancer nucleoside...
September 1, 2016: Biochemical Journal
Nicole L Williams, Pengcheng Wang, Jiabin Wu, Yinsheng Wang
Environmental exposure and endogenous metabolism can give rise to DNA alkylation. Among alkylated nucleosides, O(4)-alkylthymidine (O(4)-alkyldT) lesions are poorly repaired in mammalian systems and may compromise the efficiency and fidelity of cellular DNA replication. To cope with replication-stalling DNA lesions, cells are equipped with translesion synthesis DNA polymerases that are capable of bypassing various DNA lesions. In this study, we assessed human DNA polymerase η (Pol η)-mediated bypass of various O(4)-alkyldT lesions, with the alkyl group being Me, Et, nPr, iPr, nBu, iBu, (R)-sBu, or (S)-sBu, in template DNA by conducting primer extension and steady-state kinetic assays...
April 18, 2016: Chemical Research in Toxicology
Yidan Xu, Lei Li, Jianmin Li, Qinghuai Liu
Recent studies were mainly focus on the cytidine deaminase family genes, which contained a lot of members that varied on the function of catalytic deamination in RNA or DNA and were involved in the process of growth maintenance, host immunity, retroviral infection, tumorigenesis, and drug resistance with a feature of C-U deamination. In this study, we identified a new member of cytidine deaminase family, NYD-SP15. Previous work showed that the deduced structure of the protein contained two dCMP_cyt_deam domains, which were involved in zinc ion binding...
May 25, 2016: Gene
Jan Ludwiczak, Piotr Maj, Piotr Wilk, Tomasz Frączyk, Tomasz Ruman, Borys Kierdaszuk, Adam Jarmuła, Wojciech Rode
Endogenous thymidylate synthases, isolated from tissues or cultured cells of the same specific origin, have been reported to show differing slow-binding inhibition patterns. These were reflected by biphasic or linear dependence of the inactivation rate on time and accompanied by differing inhibition parameters. Considering its importance for chemotherapeutic drug resistance, the possible effect of thymidylate synthase inhibition by post-translational modification was tested, e.g. phosphorylation, by comparing sensitivities to inhibition by two slow-binding inhibitors, 5-fluoro-dUMP and N(4)-hydroxy-dCMP, of two fractions of purified recombinant mouse enzyme preparations, phosphorylated and non-phosphorylated, separated by metal oxide/hydroxide affinity chromatography on Al(OH)3 beads...
April 2016: Molecular BioSystems
Anna Ligasová, Radek Liboska, David Friedecký, Kateřina Mičová, Tomáš Adam, Tomáš Oždian, Ivan Rosenberg, Karel Koberna
5-Ethynyl-2'-deoxyuridine (EdU) and 5-ethynyl-2'-deoxycytidine (EdC) are mainly used as markers of cellular replicational activity. Although EdU is employed as a replicational marker more frequently than EdC, its cytotoxicity is commonly much higher than the toxicity of EdC. To reveal the reason of the lower cytotoxicity of EdC, we performed a DNA analysis of five EdC-treated human cell lines. Surprisingly, not a single one of the tested cell lines contained a detectable amount of EdC in their DNA. Instead, the DNA of all the cell lines contained EdU...
January 2016: Open Biology
I Kralova Lesna, Z Tonar, I Malek, J Maluskova, L Nedorost, J Pirk, J Pitha, V Lanska, R Poledne
Interesting and stimulating data about the effect of the perivascular adipose tissue size on atherogenesis are based mainly on CT findings. We studied this topic by directly analyzing perivascular adipose tissue in explanted hearts from patients undergoing transplantation. Ninety-six consecutive patients were included, including 58 with atherosclerotic coronary heart disease (CHD) and 38 with dilation cardiomyopathy (DCMP). The area of perivascular fat, area of the coronary artery wall, and ratio of CD68-positive macrophages within the perivascular fat and within the vascular wall were quantified by immunohistochemistry...
2015: Physiological Research
Borys Kierdaszuk
Environment of human being usually contains a high number of environmental mutagens, which may modify chemically nucleic acid bases into promutagenic analogues. Hydroxylamine (NH2OH) is a strong mutagen which modifies cytosine and adenine to N4-hydroxycytosine and N6-hydroxyadenine, respectively. Once these analogues are present in DNA or RNA, they may cause transition point mutations by the exchange between two pairs C:G and A:T into T:A and G:C, respectively. The reason for these mutations is the change of preferences between intermolecular hydrogen bonds resulting from the shift of the tautomeric equilibrium from the preferred amino form into the imino one...
2015: Postepy Biochemii
Wojciech Rode, Adam Jarmuńa
Thymidylate synthase ThyA (EC;-encoded by the Tyms gene), having been for 60 years a molecular target in chemotherapy, catalyses the dUMP pyrimidine ring C(5) methylation reaction, encompassing a transfer of one-carbon group (the methylene one, thus at the formaldehyde oxidation level) from 6R-N5,10-methylenetetrahydrofolate, coupled with a reduction of this group to the methyl one, with concomitant generation of 7,8-dihydrofolate and thymidylate. New facts are presented, concerning (i) molecular mechanism of the catalyzed reaction, including the substrate selectivity mechanism, (ii) mechanism of inhibition by a particular inhibitor, N4-hydroxy-dCMP, (iii) structural properties of the enzyme, (iv) cellular localization, (v) potential posttranslational modifications of the enzyme protein and their influence on the catalytic properties and (vi) non-catalytic activities of the enzyme...
2015: Postepy Biochemii
Ke Shi, Michael A Carpenter, Kayo Kurahashi, Reuben S Harris, Hideki Aihara
Functional and deep sequencing studies have combined to demonstrate the involvement of APOBEC3B in cancer mutagenesis. APOBEC3B is a single-stranded DNA cytosine deaminase that functions normally as a nuclear-localized restriction factor of DNA-based pathogens. However, it is overexpressed in cancer cells and elicits an intrinsic preference for 5'-TC motifs in single-stranded DNA, which is the most frequently mutated dinucleotide in breast, head/neck, lung, bladder, cervical, and several other tumor types. In many cases, APOBEC3B mutagenesis accounts for the majority of both dispersed and clustered (kataegis) cytosine mutations...
November 20, 2015: Journal of Biological Chemistry
Xiao-li Li, Jie Yuan, Yan-shan Dong, Chun-hua Fu, Mao-Teng Li, Long-jiang Yu
An HPLC method for quantifying total DNA methylation in Taxus chinensis cells is described. Optimal conditions for the method were established as follows: DNA was hydrolyzed with DNA degradase at 37°C for 3 h. The mobile phase was a mixture of Solvent A [50 mM potassium dihydrogen phosphate/triethylamine (100:0.2, v/v)] and Solvent B (methanol); the gradient was 10% (v/v) solvent B. The calibration curves for deoxycytidine monophosphate (dCMP) and methylated dCMP were linear within 1.0-160.0 µg mL(-1), with correlation coefficients of 0...
February 2016: Journal of Chromatographic Science
Amitava Adhikary, Anil Kumar, Casandra T Bishop, Tyler J Wiegand, Ragda M Hindi, Ananya Adhikary, Michael D Sevilla
In this work, iminyl σ-radical formation in several one-electron-oxidized cytosine analogs, including 1-MeC, cidofovir, 2'-deoxycytidine (dCyd), and 2'-deoxycytidine 5'-monophosphate (5'-dCMP), were investigated in homogeneous, aqueous (D2O or H2O) glassy solutions at low temperatures by employing electron spin resonance (ESR) spectroscopy. Upon employing density functional theory (DFT) (DFT/B3LYP/6-31G* method), the calculated hyperfine coupling constant (HFCC) values of iminyl σ-radical agree quite well with the experimentally observed ones, thus confirming its assignment...
September 3, 2015: Journal of Physical Chemistry. B
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