The current standard for graft rejection surveillance is endomyocardial biopsy (EMB), an invasive procedure with rare but potentially serious complications. Detection of circulating donor-derived cell-free DNA (ddcfDNA) is an option for noninvasive monitoring of graft injury and rejection. A 63-year-old man and a 65-year-old woman were monitored by EMB for allograft rejection. A total of 48 single-nucleotide polymorphisms with a minor allele frequency range of 0.4-0.5 were screened to distinguish donor and recipient DNA based on homozygosity, and digital droplet PCR was used to analyze ddcfDNA concentrations. Both subjects suffered rejection within the first 6 months after transplantation. The maximal ddcfDNA level of 270 copies (cp)/ml during EMB-confirmed acute cellular rejection (ACR; mild grade 1R/2, patient 1), and the maximal concentration of 1,846 cp/ml in the case of EMB-confirmed antibody-mediated rejection (AMR; grade 1+; patient 2), was detected. Individual monitoring of ddcfDNA dynamics from the 1st to the 6th month posttransplant reflected cardiac graft injury in patients suffering ACR or AMR, meaning that ddcfDNA may serve as a noninvasive biomarker.
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- kazuistiky MeSH
The aim of the present study was to investigate the relationship between intraocular pressure (IOP), vessel density (VD), retinal nerve fiber layer (RNFL) parameters and overall defect (OD) of the visual field in eyes where antiglaucoma treatment had not yet been initiated. A total of 61 subjects (122 eyes) who had an IOP of >20 mmHg on several occasions, in at least one eye, in routine outpatient care were included. These were subjects who had never been treated for hypertension glaucoma. The cohort was divided into four subgroups. In the first group, there were 18 eyes with an IOP value of <20 mmHg. In the second group, there were 39 eyes with IOP values of 20-22 mmHg. The third group consisted of 32 eyes with IOP values of 22-24 mmHg and the final group consisted of 33 eyes with IOP values of >24 mmHg. The IOP results were compared with VD, RNFL and OD using Pearson's correlation coefficient to assess the relationship between the selected parameters. RNFL and OD were moderately correlated only in the group of eyes with an IOP value >24 (r=0.48); in the other groups the correlation was very weak. However, changes in visual field were already observed in eyes with IOP 20-22 mmHg (r=-0.27). There was a moderate correlation in eyes with an IOP value >24 mmHg (r=-0.53). The most significant result observed was the relationship between VD and RNFL. In eyes with an IOP value ≤20, a moderate to strong correlation between these parameters was observed. This relationship increased with increasing IOP values up to a very strong correlation in the group with an IOP value >24 mmHg. A moderate to strong dependence between VD and RNFL in eyes with an IOP value ≤20 mmHg was observed, and this dependence was very strongly correlated in the eyes with an IOP value >24 mmHg.
- Publikační typ
- časopisecké články MeSH
A genetic predisposition has been identified in 30% of idiopathic pulmonary fibrosis (IPF) cases. Although it is highly probable that the genotype affects the disease susceptibility and course in almost all patients, the specific genotype goes undetected. The aim of the present study was to explore the effects of variants of the genes encoding interleukin-4 (IL-4), mucin 5B (MUC5B), toll interacting protein (TOLLIP), surfactant protein A (SFPTA), transforming growth factor-β (TGF-β) and transporters associated with antigen processing (TAP1 and TAP2) on the course of IPF. A total of 50 patients with IPF were enrolled, and variants of these genes were assessed. Lung function at the time of diagnosis and after 6, 12 and 18 months, and the number of acute exacerbations and deaths in each observation period were measured. ANOVA was used to test the association between gene polymorphisms and the decrease in lung function. There was no significant effect of the gene polymorphisms on the outcomes of patients up to 6 months during the observation period. After 12 months, an effect of an IL-4 single nucleotide polymorphism (SNP) (rs 2070874) on patient outcomes was observed [relative risk (RR) for T allele: 5.6; 95% confidence interval (CI), 0.79-39.0; P=0.053]. The RR of progression in patients with the IL-4 SNP (rs 2243250) and the CT and TT genotypes was 4.3 (95% CI, 1.1-17.5; P=0.046). A total of 18 months after the diagnosis of IPF, an effect of the TOLLIP polymorphism on patient outcome was detected (rs 111521887; risk allele GC; RR: 7.2; 95% CI, 0.97-53.6; P=0.052). Thus, IL-4 and TOLLIP gene polymorphisms may represent disease course-modifying factors, but not drivers of IPF.
- Publikační typ
- časopisecké články MeSH
The objective of the present study was to evaluate the effect of the direction of view of the eye on the postoperative near visual acuity of patients with monofocal intraocular lens. A total of 121 eyes in which we performed conventional cataract surgery with implantation of a monofocal lens were included in the study group. The postoperative examination of near visual acuity was performed at two different positions of the eye at a constant distance from the reading table, with the assumption of improving visual acuity when looking perpendicularly to the plane of the floor. The mutual relation of the postoperative parameters central keratometry (Kc), keratometry in the visual axis (KVA) and anterior chamber depth (ACD) for the single axial length ranges was determined using the correlation coefficients. In the case of vertical position of the eye (visual axis of the eye perpendicular to the floor), the uncorrected visual acuity following implantation of the monofocal lens was higher or equal compared to the horizontal position of the eye (visual axis of the eye parallel to the floor). The mean visual acuity at the horizontal position of the eye was 0.508 according to Jaeger's tables (P<0.001); at the vertical position, the mean value was 0.555 (P<0.001). Within the entire group, a weak association at best was observed between the postoperative parameters (Kc, KVA and ACD) and subsequent near visual acuity. Different dependence was found after categorising the group according to the axial length of the eye. In conclusion, the near visual acuity in eyes with an implanted monofocal lens for emmetropy to distance reached higher values at the vertical vs. horizontal position of the eyes. However, neither of the observed parameters (KC, KVA or ACD) can be unambiguously determined as decisive for the assumption of the described feature.
- Publikační typ
- časopisecké články MeSH
Kinetic and thermodynamic studies of ligand-receptor interactions are essential for increasing the understanding of receptor activation mechanisms and drug behavior. The characterization of molecular interactions on living cells in real-time goes beyond most current binding assays, and provides valuable information about the dynamics and underlying mechanism of the molecules in a living system. The effect of temperature on interactions in cell-based assays is, however, rarely discussed. In the present study, the effect of temperature on binding of monoclonal antibodies, cetuximab and pertuzumab to specific receptors on living cancer cells was evaluated, and the affinity and kinetics of the interactions were estimated at selected key temperatures. Changes in the behavior of the interactions, particularly in the on- and off-rates were observed, leading to greatly extended time to reach the equilibrium at 21°C compared with at 37°C. However, the observed changes in kinetic characteristics were less than a factor of 10. It was concluded that it is possible to conduct real-time measurements with living cells at different temperatures, and demonstrated that influences of the ambient temperature on the interaction behavior are likely to be less than one order of magnitude.
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- časopisecké články MeSH
