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Czarnecka A.M.,Military Institute of the Health Services
Journal of biomedical science | Year: 2010

Mitochondria are sub-cellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and in mitochondrial DNA (mtDNA) appear to be common features of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells, and some reports document the prevalence of inherited mitochondrial DNA polymorphisms in cancer patients. Nevertheless, a careful reanalysis of methodological criteria and methodology applied in those reports has shown that numerous papers can't be used as relevant sources of data for systematic review, meta-analysis, or finally for establishment of clinically applicable markers. In this review technical and conceptual errors commonly occurring in the literature are summarized. In the first place we discuss, why many of the published papers cannot be used as a valid and clinically useful sources of evidence in the biomedical and healthcare contexts. The reasons for introduction of noise in data and in consequence - bias for the interpretation of the role of mitochondrial DNA in the complex process of tumorigenesis are listed. In the second part of the text practical aspects of mtDNA research and requirements necessary to fulfill in order to use mtDNA analysis in clinics are shown. Stringent methodological criteria of a case-controlled experiment in molecular medicine are indicated. In the third part we suggest, what lessons can be learned for the future and propose guidelines for mtDNA analysis in oncology. Finally we conclude that, although several conceptual and methodological difficulties hinder the research on mitochondrial patho-physiology in cancer cells, this area of molecular medicine should be considered of high importance for future clinical practice. Source

Mastalerz L.,Jagiellonian University | Celinska-Lowenhoff M.,Jagiellonian University | Krawiec P.,Dietl Hospital | Batko B.,Dietl Hospital | And 2 more authors.
PLoS ONE | Year: 2015

Objectives Given reports on the increased prevalence of thromboembolic incidents in patients with eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss syndrome), we investigated whether fibrin clot properties are unfavorably altered in EGPA. Methods Ex vivo plasma fibrin clot characteristics, including clot permeability, turbidimetry and efficiency of fibrinolysis using two assays, were investigated in 34 consecutive patients with remission in EGPA according to the Birmingham Vasculitis Activity Score version 3 (23 female, 11 male), aged 48 (range, 21â€"80) years. The control group comprised 34 age- and sex- matched volunteers. Results Compared with controls, patients with EGPA were characterized by denser fiber clots (estimated pore size, Ks, 7.30±0.93 vs 10.14±1.07 109 cm2), faster fibrin polymerization (lag phase in a turbidimetric curve, 41.8±3.6 vs 47.4±2.9 s), thicker fibrin fibers (maximum absorbance, Î"Abs, 0.87±0.09 vs 0.72±0.07), higher maximum levels of D-dimer released from clots (DDmax 4.10±0.46 vs 3.54±0.35 mg/L), and prolonged clot lysis time (t50%; 9.50±1.45 vs 7.56±0.87 min); all p<0.0001. Scanning electron microscopy images confirmed denser plasma fibrin networks composed of thinner fibers formed in EGPA. Antineutrophil cytoplasmic antibody status and C-reactive protein did not affect clot variables. Multivariate analysis adjusted for fibrinogen showed that Ks was predicted by eosinophil count, peak thrombin generation, factor VIII, and soluble CD40 ligand, whereas eosinophil count, peak thrombin generation and antiplasmin predicted t50%. Conclusion This study is the first to show that EGPA is associated with prothrombotic plasma fibrin clot phenotype, which may contribute to thromboembolic manifestations reported in this disease. © 2015 Mastalerz et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source

Kukwa W.,Medical University of Warsaw | Ozieblo A.,Medical University of Warsaw | Scinska A.,Medical University of Warsaw | Czarnecka A.M.,Military Institute of the Health Services | And 2 more authors.
Oncology Letters | Year: 2010

For osteoblastoma, with its predilection for the spinal column and appendicular skeleton, the skull is an unusual site, and paranasal sinus involvement is very rare. Herein, we report on a case in which the disease was located within the sphenoid bone. To the best of our knowledge, this is the 4th reported case of osteoblastoma with a sphenoid origin (1). We report an osteoblastoma of the sphenoid sinus in a 12-year-old girl who presented with exophthalmos. Computed tomography (CTCT) demonstrated an expansile lesion of the sphenoid which caused the orbital contents to be compressed and deviated to the right. In the magnetic resonance imaging scan, the lesion was found to invade the cranial base in the frontal and temporal region, approximating to the cavernous sinus and internal carotid artery on the right. Bilateral fronto-orbital craniotomy was performed. Histologically, the lesion was composed of proliferating osteoblasts along with vascular stroma. The tumor was described as an aggressive osteoblastoma. In the follow-up CTCT four months later, a pathological mass was observed in the area of the nasal septum, and a signal void was present on all sequences in the densely sclerotic areas. A second resection was performed. The patient has been disease-free for 61 months. Herein, we present the diagnosis and management of this unusual lesion. The histopathology and the imaging characteristics are shown. Source

Kisiel B.M.,Military Institute of the Health Services | Kosinska J.,Medical University of Warsaw | Wierzbowska M.,Institute of Rheumatology | Rutkowska-Sak L.,Institute of Rheumatology | And 9 more authors.
Lupus | Year: 2011

Oestrogens acting via nuclear receptors (encoded by ESR1 or ESR2) are important for pathogenesis of systemic lupus erythematosus (SLE). rs2234693 and rs4986938 are two single nucleotide polymorphisms (SNPs) whose C and A variants increase transcription of ESR1 and ESR2, respectively. The T allele of rs2234693 was associated with early onset SLE, whereas the role of rs4986938 in SLE was not reported. Our aim was to examine the role of rs2234693 and rs4986938 in conferring susceptibility to juvenile and adult SLE (jSLE and aSLE). Genotype distribution of both SNPs was analysed in 84 jSLE, 112 aSLE patients and 1001 controls. Allele C of rs2234693 was associated with jSLE (OR = 1.87, p = 0.006, pcorrected = 0.02), whereas allele A of rs4986938 showed an association with aSLE (OR = 1.46, p = 0.008, pcorrected = 0.03). In jSLE, rs2234693 C had lower frequency in patients with central nervous system involvement (OR = 0.39, p = 0.005, pcorrected = 0.04) and showed a trend for increase among males, patients with renal involvement and those without DR2/3 (p < 0.05, pcorrected > 0.05). Whereas our results are consistent with a role of ESR1 variation in jSLE, more studies are needed since the direction of association was the opposite of that reported previously. The association between rs4986938 (ESR2) and aSLE is a novel finding, consistent with our recent report associating this variant with Graves' disease. © The Author(s), 2011. Source

Markiewicz T.,Warsaw University of Technology | Markiewicz T.,Military Institute of the Health Services | Grala B.,Military Institute of the Health Services | Kozlowski W.,Military Institute of the Health Services | And 2 more authors.
Analytical and Quantitative Cytology and Histology | Year: 2010

OBJECTIVE: To present a computerized system for cell counting in histopathologic slides of meningioma and oligodendroglioma stained immunohistochemically against Ki-67 antigen and discuss the variability of tumor cell numbers in the field of view of analyzed neoplasms to standardize tumor cellularity. STUDY DESIGN: A computer program using an algorithm based on mathematical morphology was developed to perform quantitative evaluation of slides. That solution was combined with the Support Vector Machine used for classification of cell immunoreactivity. RESULTS: The mean number of cells in the analyzed field of view from patients with meningioma was 623. Of these, 95% were in the 386-781 cells range. In oligodendrogliomas the mean was 474 cells and all results were in the 204-736 range. The mean relative discrepancy between results of our system and human expert score was 8%. CONCLUSION: The proposed system appeared to be an efficient tool for supporting histopathologic diagnosis. The applied sequential thresholding simulated well the human process of cell recognition. Cellularity of the analyzed tumors did not show stability within the specimens from different patients. The results were also highly variable in different fields of view obtained from the same patient. © Science Printers and Publishers, Inc. Source

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