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Ragauskas S.,University of Eastern Finland | Ragauskas S.,Vilnius Gediminas Technical University | Ragauskas S.,State Research Institute for Innovative Medicine | Ragauskas S.,Experimentica Ltd. | And 12 more authors.
PLoS ONE | Year: 2014

Huntington's disease (HD) is an inherited neurodegenerative disorder that primarily affects the medium-size GABAergic neurons of striatum. The R6/2 mouse line is one of the most widely used animal models of HD. Previously the hallmarks of HDrelated pathology have been detected in photoreceptors and interneurons of R6/2 mouse retina. Here we aimed to explore the survival of retinal ganglion cells (RGCs) and functional integrity of distinct retinal cell populations in R6/2 mice. The pattern electroretinography (PERG) signal was lost at the age of 8 weeks in R6/2 mice in contrast to the situation in wild-type (WT) littermates. This defect may be attributable to a major reduction in photopic ERG responses in R6/2 mice which was more evident in b-than a-wave amplitudes. At the age of 4 weeks R6/2 mice had predominantly the soluble form of mutant huntingtin protein (mHtt) in the RGC layer cells, whereas the aggregated form of mHtt was found in the majority of those cells from the 12-week-old R6/2 mice and onwards. Retinal astrocytes did not contain mHtt deposits. The total numbers of RGC layer cells, retinal astrocytes as well as optic nerve axons did not differ between 18-week-old R6/2 mice and their WT controls. Our data indicate that mHtt deposition does not cause RGC degeneration or retinal astrocyte loss in R6/2 mice even at a late stage of HDrelated pathology. However, due to functional deficits in the rod- and conepathways, the R6/2 mice suffer progressive deficits in visual capabilities starting as early as 4 weeks; at 8 weeks there is severe impairment. This should be taken into account in any behavioral testing conducted in R6/2 mice. Copyright: © 2014 Ragauskas et al.

Podoliankaite M.,Lithuanian Academy of Sciences | Luksa J.,Lithuanian Academy of Sciences | Vysniauskis G.,Lithuanian Academy of Sciences | Vysniauskis G.,State Research Institute for Innovative Medicine | And 6 more authors.
Molecular Biotechnology | Year: 2014

Saccharomyces cerevisiae K2 toxin is a highly active extracellular protein, important as a biocontrol agent for biotechnological applications in the wine industry. This protein is produced at negligible levels in yeast, making difficult to isolate it in amounts sufficient for investigation and generation of analysis tools. In this work, we demonstrate the use of a bacterial system for expression of the recombinant K2 protein, suitable for generation of antibodies specific for toxin of the yeast origin. Synthesis of the full-length S. cerevisiae K2 preprotoxin in Escherichia coli was found to be toxic to the host cell, resulting in diminished growth. Such effect was abolished by the introduction of the C-terminal truncation into K2 protein, directing it into non-toxic inclusion body fraction. The obtained protein is of limited solubility thus, facilitating the purification by simple and efficient chromatography-free procedure. The protein aggregates were successfully refolded into a soluble form yielding sufficient amounts of a tag-less truncated K2 protein suitable for polyclonal antibody production. Antibodies were raised in rabbit and found to be specific for detection of both antigen and native S. cerevisiae K2 toxin. © 2014 Springer Science+Business Media.

Denkovskij J.,State Research Institute Center for Innovative Medicine | Rudys R.,State Research Institute for Innovative Medicine | Bernotiene E.,State Research Institute Center for Innovative Medicine | Minderis M.,Vilnius University | And 2 more authors.
Cytometry Part A | Year: 2015

The aim of present study was to assess the expression of surface markers and the accumulation of protoporphyrin IX in synovial mesenchymal stem cells (SMSCs). SMSC from patients with rheumatoid arthritis (RA, n=5) and osteoarthritis (OA, n=5-6) were characterized and their PpIX accumulation rates were evaluated by flow cytometry. The expression of the 21 out of 24 tested surface markers, related to stem-like features and aggressiveness of cells showed no statistically significant differences between RA and OA groups. However, the cells from RA group had the significantly lower levels of expression for the integrin-associated protein CD47 and the grow factor receptor CD271 (P=0.018), while the higher levels of cell membrane zinc-dependent metalloproteinase CD10 (P=0.006), as compared to the cells from OA group. Comparison of the mean intensities of PpIX fluorescence revealed no statistically significant differences between the RA and OA groups, as well as no relation to proliferation rates or cell size, although some conspicuous distinction in PpIX accumulation was observed in certain specimens within these groups, suggesting possibilities of this method application for characterization of individual SMSC populations. CD10, CD47, and CD271 were differently expressed in RA and OA SMSC, while had no direct association with the PpIX fluorescence intensity. © 2015 International Society for Advancement of Cytometry.

Dadoniene J.,Vilnius University | Dadoniene J.,State Research Institute for Innovative Medicine | Miglinas M.,Vilnius University | Miltiniene D.,Vilnius University | And 4 more authors.
World Journal of Surgical Oncology | Year: 2016

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterised by severe hypophosphataemia and osteomalacia, with renal phosphate wasting that occurs in association with tumour. The epidemiology likewise aetiology is not known. The clinical presentation of TIO includes bone fractures, bone and muscular pains, and sometimes height and weight loss. TIO may be associated with mesenchymal tumours which may be benign or malignant in rare cases. Mesenchymal tumour itself may be related to fibroblast growth factor 23 (FGF23), which is responsible for hypophosphataemia and phosphaturia occurring in this paraneoplastic syndrome. Hypophosphataemia, phosphaturia and elevated alkaline phosphatase are the main laboratory readings that may lead to more precise investigations and better diagnosis. Finding the tumour can be a major diagnostic challenge and may involve total body magnetic resonance imaging, computed tomography and scintigraphy using radiolabelled somatostatin analogue. The treatment of choice for TIO is resection of a tumour with a wide margin to insure complete tumour removal, as recurrences of these tumours have been reported. We provide here an overview on the current available TIO case reports and review the best practices that may lead to earlier recognition of TIO and the subsequent treatment thereof, even though biochemical background and the long-term prognosis of the disease are not well understood. This review also includes a 4-year-long history of a patient that featured muscular pains, weakness and multiple stress fractures localised in the hips and vertebra with subsequent recovery after tumour resection. Because the occurrence of such a condition is rare, it may take years to correctly diagnose the disease, as is reported in this case report. © 2016 Dadoniene et al.

Dadoniene J.,Vilnius University | Dadoniene J.,State Research Institute for Innovative Medicine | Stropuviene S.,Vilnius University | Stropuviene S.,State Research Institute for Innovative Medicine | And 4 more authors.
Medicina (Lithuania) | Year: 2015

Background and objective: Increased mortality and shorter survival among rheumatoid arthritis (RA) patients are recognized but not fully explained. This cohort study aimed to identify predictors of mortality among RA patients at a tertiary clinical setting. Materials and methods: Patients with RA were recruited during 1998-2003 and followed up until April 1, 2012, or death whichever happened first. Baseline variables included sociodemographic and disease characteristics, and comorbidities. Cox regression and hazard risk (HR) were computed to estimate risks for mortality. Results: One hundred ninety-one patients were included into the study, 186 patients were eligible for the analysis and of these 131 patients (70.4%) completed the entire period of followed-up while 55 patients (29.6%) died. The average follow up period was equivalent to 9.24 year per person. A Cox regression model identified four major factors having an impact on survival. History of a stroke at baseline was identified as a major factor (HR = 5.33; 95% CI, 2.13-13.32). Statistically significant risk factors were also age over 50 years (HR = 4.59; 95% CI, 2.04-10.30); education less than 11 years (HR = 3.3; 95% CI, 1.72-6.33) and angina pectoris (HR = 1.98; 95% CI, 1.03-3.80). Conclusions: Higher age, lower education and cardiovascular comorbidities were identified as predictors of mortality in this prospective cohort study while disease-related variables were not independent predictors of mortality. © 2014 Lithuanian University of Health Sciences.

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