The article is calassified as top publication in a journal ranking second in the field. Primary hepatocytes are an important in vitro model for studying metabolism inman. Caspase-9 and Bax are regulators of apoptotic pathway. Here we report on the translocation of procaspase-9 and Bax from cytoplasm to nuclei as well as on dispersion of mitochondria; these processes occur after isolation of primary hepatocytes. The observed changes appear similar to those at the beginning of apoptosis, however, the isolated hepatocytes are not apoptotic for the following reasons: (1) cells have a normal morphology and function; (2) the mitochondria are energized; (3) there is no apoptosis unless it is induced by e.g. staurosporine or nodularin. Staurosporine does not trigger apoptosis through activation of caspase-9, as its activity is detected later than that of caspase-3. We propose that the translocation of procaspase-9 and Bax into the nuclei reduces the ability to trigger apoptosis through the intrinsic apoptotic pathway. The shifts of procaspase-9 and Bax are reversiblein the absence of the apoptotic trigger; the spontaneous reversion was confirmed experimentally for procaspase-9, while Bax shifted from the nuclei to the cytosol and mitochondria after the initiation of apoptosis. To distinguish this process from apoptosis, we call it pre-apoptotic cell stress response. It shares some features with apoptosis, however, it is reversible and apoptosis has to be induced in addition to this process. Knowledge on pre-apoptotic cell stress response is important for assessing the quality of the cells used in cell therapies, in regenerative medicine and of those used for modelling metabolic processes.
COBISS.SI-ID: 26839513
We present a novel approach for generating information about a voxel's tissue class membership based on its signature--a collection of local image textures estimated over a range of neighborhood sizes. The approach produces a form of tissue class priors that can be used to initialize and regularize image segmentation. The signature-based approach is a departure from current location-based methods, which derive tissue class likelihoods based on a voxel's location in standard template space. To use location-based priors, one needs to register the volume in question to the template space, and estimate the image intensity bias field. Two optimizations, over more than a thousand parameters, are needed when high order nonlinear registration is employed. In contrast, the signature-based approach is independent of volume orientation, voxel position, and largely insensitive to bias fields. For thesereasons, the approach does not require the use of population derived templates. The prior information is generated from variations in image texturestatistics as a function of spatial scale, and an SVM approach is used to associate signatures with tissue types. With the signature-based approach, optimization is needed only during the training phase for the parameter estimation stages of the SVM hyperplanes, and associated PDFs; a training process separate from the segmentation step. We found that signature-based priors were superior to location-based ones aligned under favorable conditions, and that signature-based priors result in improved segmentation when replacing location-based ones in FAST (Zhang et al., 2001), a widely usedsegmentation program. The software implementation of this work is freely available as part of AFNI http://afni.nimh.nih.gov. Journal rank: first in the field of neuroimaging and first quarter in the field of neuroscience.
COBISS.SI-ID: 28180185
The article was published in the journal ranking first in the field. Background: Contemporary ventricular assist device therapy results in a high rate of successful heart transplantation but is associated with bleeding, infections, and other complications. Further reductions in pump size, centrifugal design, and intrapericardial positioning may reduce complications and improve outcomes. Methods and results: We studied a small, intrapericardially positioned, continuous-flow centrifugal pump in patients requiring an implanted ventricular assist device as a bridge to heart transplantation. The course of investigational pump recipients was compared with that of patients implanted contemporaneously with commercially available devices. The primary outcome, success, was defined as survival on the originally implanted device, transplantation, or explantation for ventricular recovery at 180 days and was evaluated for both noninferiority and superiority. Secondary outcomes included a comparison of survival between groups and functional and quality-of-life outcomes and adverse events in the investigational device group. A total of 140 patients received the investigational pump, and 499 patients received a commercially available pump implanted contemporaneously. Success occurred in 90.7% of investigational pump patients and 90.1% of controls, establishing the noninferiority of the investigational pump (P(0.001; 15% noninferiority margin). At 6 months, median 6-minute walk distance improved by 128.5 m, and both disease-specific and global quality-of-life scores improved significantly. Conclusions: A small, intrapericardially positioned, continuous-flow, centrifugal pump was noninferior to contemporaneously implanted, commercially available ventricular assist devices. Functional capacity and quality of life improved markedly, and the adverse event profile was favorable.
COBISS.SI-ID: 30523353
BACKGROUND: We investigated the effects of transendocardial CD34(+) cell transplantation in patients with ischemic cardiomyopathy. METHODS AND RESULTS: In a prospective crossover study, we enrolled 33 patients with ischemic cardiomyopathy with left ventricular ejection fraction (40%. In phase 1, patients were treated with medical therapy for 6 months. Thereafter, all patients underwent transendocardial CD34(+) cell transplantation. Peripheral blood CD34(+) cells were mobilized by granulocyte colony stimulating factor, collected via apheresis, and injected transendocardially in the areas of hibernating myocardium. Patients were followed up for 6 months after the procedure (phase 2). Two patients died during phase 1 and none during phase 2. The remaining 31 patients were 85% men, aged 57±6 years. In phase 1, we found no change in left ventricular ejection fraction, N-terminal pro B-type natriuretic peptide or 6-minute walk distance. In contrast, in phase 2 there was an improvement in left ventricular ejection fraction increase in 6-minute walk distance, and a decrease in N-terminal pro B-type natriuretic peptide. The average number of injected CD34(+) cells was 90.6±7.5×10(6). Higher doses of CD34(+) cells and a more diffuse distribution of transendocardial cell injections were associated with better clinical response. CONCLUSIONS:Transendocardial CD34(+) cell transplantation may be associated with improved left ventricular function, decreased N-terminal pro B-type natriuretic peptide levels, and better exercise capacity in patients with ischemic cardiomyopathy. These effects seem to be particularly pronounced in patients receiving diffusely distributed cell injections and high-dose cell therapy.
COBISS.SI-ID: 1661612
Functional and structural brain alterations in the absence of the auditory input have been described, but the observed structural brain changes in the deaf are not uniform. Some of the previous researchers focused only on the auditory areas, while others investigated the whole brain or other selected regions of interest. Majority of studies revealed decreased white matter (WM) volume or altered WM microstructure and preserved grey matter (GM) structure of the auditory areas in the deaf. However, preserved WM and increased or decreased GM volume of the auditory areas in the deaf have also been reported. Several structural alterations in the deaf were found also outside the auditory areas, but these regions differ between the studies. The observed differences between the studies could be due to the use of different single-analysis techniques, or the diverse population sample and its size, or possibly due to the usage of hearing aids by some participating deaf subjects. To overcome the aforementioned limitations four different image-processing techniques were used to investigate changes in the brain morphology of prelingually deaf adults who have never used hearing aids. GM and WM volume of the Heschl's gyrus (HG) were measured using manual volumetry, while whole brain GM volume, thickness and surface area were assessed by voxel-based morphometry (VBM) and surface-based analysis. The microstructural properties of the WM were evaluated by diffusion tensor imaging (DTI). The data were compared between 14 congenitally deaf adults and 14 sex- and age-matched normal hearing controls. Manual volumetry revealed preserved GM volume of the bilateral HG and significantly decreased WM volume of the left HG in the deaf. VBM showed increased cerebellar GM volume in the deaf, while no statistically significant differences were observed in the GM thickness or surface area between the groups. The results of the DTI analysis showed WM microstructural alterations between the groups in the bilateral auditory areas, including the superior temporal gyrus, the HG, the planum temporale and the planum polare, which were more extensive in the right hemisphere. Fractional anisotropy (FA) was significantly reduced in the right and axial diffusivity (AD) in the left auditory areas in the deaf. FA and AD were significantly reduced also in several other brain areas outside the auditory cortex in the deaf. The use of four different methods used in our study, although showing changes that are not directly related, provides additional information and supports the conclusion that in prelingually deaf subjects structural alterations are present both in the auditory areas and elsewhere. Our results support the findings of those studies showing that early deafness results in decreased WM volume and microstructural WM alterations in the auditory areas. As we observed WM microstructural alteration also in several other areas and increased GM volume in the cerebellum in the deaf, we can conclude that early deafness results in widespread structural brain changes. These probably reflect atrophy or degradation as well as compensatory cross-modal reorganisation in the absence of the auditory input and the use of the sign language.
COBISS.SI-ID: 1849516