30 research outputs found
The Regulation of Commodity Options
To outline further genetic mechanisms of transformation from follicular lymphoma (FL) to diffuse large B-cell lymphoma (DLBCL), we have performed whole genome array-CGH in 81 tumors from 60 patients [29 de novo DLBCL (dnDLBCL), 31 transformed DLBCL (tDLBCL), and 21 antecedent FL]. In 15 patients, paired tumor samples (primary FL and a subsequent tDLBCL) were available, among which three possessed more than two subsequent tumors, allowing us to follow specific genetic alterations acquired before, during, and after the transformation. Gain of 2p15-16.1 encompassing, among others, the REL, BCL11A, USP34, COMMD1, and OTX1 genes was found to be more common in the tDLBCL compared with dnDLBCL (P < 0.001). Furthermore, a high-level amplification of 2p15-16.1 was also detected in the FL stage prior to transformation, indicating its importance during the transformation event. Quantitative real-time PCR showed a higher level of amplification of REL, USP34, and COMMD1 (all involved in the NF kappa B-pathway) compared with BCL11A, which indicates that the altered genes disrupting the NF kappa B pathway may be the driver genes of transformation rather than the previously suggested BCL11A. Moreover, a 17q21.33 amplification was exclusively found in tDLBCL, never in FL (P < 0.04) or dnDLBCL, indicating an upregulation of genes of importance during the later phase of transformation. Taken together, our study demonstrates potential genomic markers for disease progression to clinically more aggressive forms. We also confirm the importance of the TP53-, CDKN2A-, and NF kappa B-pathways for the transformation from FL to DLBCL
Unexpected Routes of the Mutagenic Tautomerization of the T Nucleobase in the Classical AĀ·T DNA Base Pairs: A QM/QTAIM Comprehensive View
In this paper using quantum-mechanical (QM) calculations in combination with Bader's quantum theory of āAtoms in Moleculesā (QTAIM) in the continuum with Īµ = 1, we have theoretically demonstrated for the first time that revealed recently highly-energetic conformers of the classical AĀ·T DNA base pairs ā Watson-Crick [AĀ·T(wWC)], reverse Watson-Crick [AĀ·T(wrWC)], Hoogsteen [AĀ·T(wH)] and reverse Hoogsteen [AĀ·T(wrH)] ā act as intermediates of the intrapair mutagenic tautomerization of the T nucleobase owing to the novel tautomerisation pathways: AĀ·T(wWC)āAĀ·T*(wā„WC); AĀ·T(wrWC)āAĀ·TO2*(wā„rWC); AĀ·T(wH)āAĀ·T*(wā„H); AĀ·T(wrH)āAĀ·TO2*(wā„rH). All of them occur via the transition states as tight ion pairs (A+, protonated by the N6H2 amino group)Ā·(Tā, deprotonated by the N3H group) with quasi-orthogonal geometry, which are stabilized by the participation of the strong (A)N6+HĀ·Ā·Ā·O4ā/O2ā(T) and (A)N6+HĀ·Ā·Ā·N3ā(T) H-bonds. Established tautomerizations proceed through a two-step mechanism of the protons moving in the opposite directions along the intermolecular H-bonds. Initially, proton moves from the N3H imino group of T to the N6H2 amino group of A and then subsequently from the protonated N6+H3 amino group of A to the O4/O2 oxygen atom of T, leading to the products ā AĀ·T*(wā„WC), AĀ·TO2*(wā„rWC), AĀ·T*(wā„H), and AĀ·TO2*(wā„rH), which are substantially non-planar, conformationally-labile complexes. These mispairs are stabilized by the participation of the (A)N6H/N6H'Ā·Ā·Ā·N3(T) and (T)O2H/O4HĀ·Ā·Ā·N6(A) H-bonds, for which the pyramidalized amino group of A is their donor and acceptor. The Gibbs free energy of activation of these mutagenic tautomerizations lies in the range of 27.8ā29.8 kcalĀ·molā1 at T = 298.15 K in the continuum with Īµ = 1
Clinical, genetic, and immunohistochemical characterization of 70 Ukrainian adult cases with post-Chornobyl papillary thyroid carcinoma
Papillary thyroid carcinoma (PTC) exhibits various molecular abnormalities, both
when sporadic and radiation-related. PTC is still diagnosed in adult individuals who
were younger than 18 years at the time of the Chornobyl accident in 1986 and lived
within the contaminated area. The preoperative diagnosis of PTC is based on
ultrasound-guided fine needle aspiration cytology (FNAC), which is highly informative
in up to 90% of biopsies. FNAC is not informative for the discrimination of follicular
thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA). Moreover, FNAC is
often unreliable for diagnosis of cystic PTC due to its common presentation as a mural
nodule in a cystic mass. In case of cystic PTC, biopsy sometimes reveals a cystic fluid
containing insufficient amount of representative cells for cytology.
In this work, PTC was characterized in relation to irradiation from radioactivity at
childhood. Possible preoperative diagnostic markers for discrimination between PTC
and other follicular thyroid neoplasms were identified, and their validity was tested.
In Study I molecular, genetic and clinical characteristics in 70 post-Chornobyl
PTCs were investigated. A common BRAF 1799T>A mutation was detected in 26 cases,
overrepresentation of RET/PTC1 in 20 whereas RET/PTC3 was found in 4 cases. BRAF
mutation was observed 3.5 times less frequent in the PTC accompanied by chronic
lymphocytic thyroiditis (PTC/CLT) as compared to PTC only (12% vs. 44%). Greater
expression of cyclin A was observed in PTC ā„ 2 cm as compared to PTC < 2 cm (1.2%
vs. 0.6%). In conclusion, BRAF mutation and RET/PTC1 rearrangement as well as other
molecular features of adult post-Chornobyl PTC were partly overlapping with other
reported PTC cohorts.
In Study II the SELDI-TOF mass spectrometry method was applied for PTC, FTC,
FTA and normal thyroid tissue (NT). Significant overexpression of the protein S100A6
was identified in PTC as compared to FTC, FTA and NT (p < 0.05). This result was
verified both by Western blot (WB), using the same samples, and by IHC in these and
additionally in the PTC samples investigated in Study I. Moreover, the presence of two
post-translational modifications of S100A6 was observed and verified by LC-MS/MS.
S100A6 expression is strongly associated with PTC, and can therefore be tested for
discrimination between follicular thyroid tumors and PTC.
In Study III a two dimensional gel electrophoresis followed by MALDI-TOF mass
spectrometry for proteomic profiling of PTC, FTC and FTA was performed. 25 protein
spots showing significantly different expression between studied groups were identified.
Of these, 9 protein spots were selected for further analyses by WB using the initially
studied samples and by IHC using these as well as samples from Study I. The findings
suggest additional proteins to be deregulated in thyroid tumors, and their clinical
significance can now be further studied.
In Study IV preoperative diagnostic markers for PTC in cystic lesions were
identified by applying LC-MS/MS method. Out of all 1581 identified proteins, annexin
A3 (ANXA3), carboxymethylenebutenolidase homolog (CMBL) cytokeratin 19 (CK-
19) and S100A13 were selected for validation by IHC and WB. ANXA3 and CMBL
showed overexpression in both controls and PTCs, whereas S100A13 and CK-19 were
up-regulated in PTC only (p < 0.05), suggesting their possible role for discrimination
between cystic PTC and benign thyroid cysts
Cardiovascular complications secondary to Graves' disease: a prospective study from Ukraine.
Graves' disease (GD) is a common cause of hyperthyroidism resulting in development of thyrotoxic heart disease (THD).to assess cardiovascular disorders and health related quality of life (HRQoL) in patients with THD secondary to GD.All patients diagnosed with THD secondary to GD between January 2011 and December 2013 were eligible for this study. Clinical assessment was performed at baseline and at the follow-up visit after the restoring of euthyroid state. HRQoL was studied with a questionnaire EQ-5D-5L.Follow-up data were available for 61 patients, but only 30 patients with THD secondary to GD were consented to participate in investigation of their HRQoL. The frequency of cardiovascular complications was significantly reduced as compared before and after the antithyroid therapy as follows: resting heart rate (122 vs. 74 bpm), blood pressure: systolic (155 vs. 123 mm Hg), diastolic (83 vs. 66 mm Hg), supraventricular premature contractions (71% vs. 7%), atrial fibrillation (72% vs. 25%), congestive heart failure (69% vs. 20%), thyrotoxic cardiomyopathy (77% vs. 26%), all p<0.01. Anti-TSH receptor antibodies were determined as independent predictor of left ventricular geometry changes, (b-coefficient = 0.04, 95%CI 0.01-0.07, p = 0.02). HRQoL was improved in all domains and self-rated health increased from 43 to 75 units by visual analogue score (p<0.001).Restoring of euthyroid state in patients with GD is associated with significant elimination of cardiovascular disorders and improvement of HRQoL. To our knowledge this is the first study evaluating Ukrainian patients with THD secondary to GD with focus on HRQoL
Prognostic role of increased serum homocysteine concentration in preeclampsia
Objective: To assess homocysteine (Hcy) concentration in women with preeclampsia (PE). Methods: Hcy concentrations were detected by ELISA in 305 pregnancies. Results: Hcy concentration in patients with PE was 16.07 umol/L at 10ā14Ā weeks as compared to 7.19 umol/L in normotensive pregnancies (pĀ 9.55 umol/L with area under curve of 0.859, sensitivity of 91.67%, specificity of 72.24%. Conclusion: Assessment of serum Hcy concentration may be used as a predictor of PE, with the highest diagnostic utility in the first trimester of pregnancy
Unexpected Routes of the Mutagenic Tautomerization of the T Nucleobase in the Classical AĀ·T DNA Base Pairs: A QM/QTAIM Comprehensive View
Medications for treatment of cardiological complications before the antithyroid therapy and after the follow-up.
<p>Medications for treatment of cardiological complications before the antithyroid therapy and after the follow-up.</p
Health related quality of life assessed by the EQ-5D-5L instrument.
<p>Health related quality of life assessed by the EQ-5D-5L instrument.</p
Analyses of cardiovascular parameters before and after the antithyroid therapy in patients with Gravesā disease.
<p>Analyses of cardiovascular parameters before and after the antithyroid therapy in patients with Gravesā disease.</p