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Biomedical subjects

M Woźniak

Publications and source records attributed to M Woźniak.

At least 19 recordsLinked to original sources
PubMed2006

Lack of association between the TNF-alpha promoter gene polymorphism and susceptibility to B-cell chronic lymphocytic leukaemia.

B-cell chronic lymphocytic leukaemia (B-CLL) is a lymphoproliferative disorder characterized by clonal expansion of B lymphocytes. The present study aimed to determine whether there is an association between the polymorphic features located within the promoter/enhancer region of tumour necrosis factor-alpha (TNFA) gene and susceptibility to B-CLL. TNFA (-308 G/A) promoter single nucleotide polymorphism (SNP) was determined by polymerase chain reaction with sequence-specific primers (PCR-SSP) using commercial oligonucleotides. No significant association was found between the distribution of TNFA alleles and B-CLL in Polish patients with B-CLL. Our single centre results were compared with other literature data and combined in a cumulative analysis employing the Mantel-Haenszel method. Among 183 B-CLL patients, 47 (26%) were carrying TNFA*2 allele and this allele was present in 98 out of 348 controls (28%). Also, the results of the Mantel-Haenszel test did not show a significant correlation [Mantel-Haenszel estimate of approximate relative risk (RMH) = 0.86, P = 0.294]. These results suggest that TNFA (-308) alleles are not involved in the predisposition to the development of B-CLL.

Adult↗
PubMed2005

Mimicking of glutathione peroxidase deficiency by exposition of JAR cells to increased level of synthetic hydroperoxide.

A short chain synthetic analogue of lipid hydroperoxides was used to overload glutathione peroxidase (GPx) in human choriocarcinoma cell line JAR cells. Cells exposed to 100 microM tBuOOH displayed a 40% reduction in ATP level and significantly increased in membrane permeability, visualised by the lactate dehydrogenase (LDH) release into the extracellular medium. The intracellular level of oxygen free radicals measured as an oxidation of the dichlorodihydro-fluorescein diacetate (H2DCF-DA) significantly increased after 2 hours of cell exposition to 100 microM tBuOOH. Concomitantly MDA, 4-HNE level increased to 2 nmol/mg of cell protein after 2 hours. Mitochondria stained with MitoTracker Red CMXRos displayed a filamentous appearance in control cells but changed into granular less energised organelles after exposition to tBuOOH. Collectively, the above results indicate the importance of the contribution of oxidative stress in the development of pre-eclampsia.

Adenosine Triphosphate↗
PubMed2004

Survivin expression in lymph nodes, affected by lymphoma and reactive hyperplasia.

Survivin is a member of the inhibitors from the apoptosis family over-expressed in various human cancers. The aim of the study was to evaluate the expression of survivin in lymph nodes, invaded by non-Hodgkin's lymphomas (nHL) and in lymph nodes reactive hyperplasia. We analysed paraffin sections obtained from 50 patients with nHL and from 13 patients with reactive hyperplasia using, an anti-survivin antibody. There was abundant immunoreactivity cytoplasm in 34/50 (68%) patients with nHL and in only 5/13 (38%) with reactive hyperplasia. Out of the 27 patients with aggressive nHL, 19 (70%) revealed survivin expression in almost all tumour cells. Out of the 23 patients with indolent nHL, 16 (70%) revealed the expression but with lower immunoreactivity score. The study indicates that patients with nHL presented a high level of survivin expression, it was more pronounced in aggressive than in indolent nHL.

Humans↗
PubMed2003

Diversity of mitochondrial DNA lineages in South Siberia.

To investigate the origin and evolution of aboriginal populations of South Siberia, a comprehensive mitochondrial DNA (mtDNA) analysis (HVR1 sequencing combined with RFLP typing) of 480 individuals, representing seven Altaic-speaking populations (Altaians, Khakassians, Buryats, Sojots, Tuvinians, Todjins and Tofalars), was performed. Additionally, HVR2 sequence information was obtained for 110 Altaians, providing, in particular, some novel details of the East Asian mtDNA phylogeny. The total sample revealed 81% East Asian (M*, M7, M8, M9, M10, C, D, G, Z, A, B, F, N9a, Y) and 17% West Eurasian (H, U, J, T, I, N1a, X) matrilineal genetic contribution, but with regional differences within South Siberia. The highest influx of West Eurasian mtDNAs was observed in populations from the East Sayan and Altai regions (from 12.5% to 34.5%), whereas in populations from the Baikal region this contribution was markedly lower (less than 10%). The considerable substructure within South Siberian haplogroups B, F, and G, together with the high degree of haplogroup C and D diversity revealed there, allows us to conclude that South Siberians carry the genetic imprint of early-colonization phase of Eurasia. Statistical analyses revealed that South Siberian populations contain high levels of mtDNA diversity and high heterogeneity of mtDNA sequences among populations (Fst = 5.05%) that might be due to geography but not due to language and anthropological features.

DNA, Mitochondrial↗
PubMed2002

Protein oxidation in male Syrian hamster kidney during estrogen-induced carcinogenesis.

Chronic administration of estradiol leads to generation of estrogen-dependent renal cancer in male Syrian hamsters within 9-12 months. The pathogenesis of this tumour is associated with oxygen free radicals, however, it is still not clear which metabolic pathway of estrogens is responsible for the generation of the radicals, and which part of the cell is mostly affected by it. The paper presents an experiment in which the protein oxidation measured by carbonyl groups level in 9-month estrogenization scheme. The level of carbonyl groups was significantly elevated starting from the 1st month of estrogenization until the 9th. The weight of the kidneys reflecting possible tumuorigenesis was also significantly increased in estrogenized group starting at the 2nd month of the experiment. The weight of the testes, a sign of adequate estrogenicity, was decreased dramatically in the estrogenized group from the first to the last month of experiment. The results suggest that the kidney of estrogenized male Syrian hamster suffers from oxidative stress affecting proteins.

Journal Article↗
PubMed2002

Mitochondrial DNA variability in Poles and Russians.

Mitochondrial DNA (mtDNA) sequence variation was examined in Poles (from the Pomerania-Kujawy region; n = 436) and Russians (from three different regions of the European part of Russia; n = 201), for which the two hypervariable segments (HVS I and HVS II) and haplogroup-specific coding region sites were analyzed. The use of mtDNA coding region RFLP analysis made it possible to distinguish parallel mutations that occurred at particular sites in the HVS I and II regions during mtDNA evolution. In total, parallel mutations were identified at 73 nucleotide sites in HVS I (17.8%) and 31 sites in HVS II (7.73%). The classification of mitochondrial haplotypes revealed the presence of all major European haplogroups, which were characterized by similar patterns of distribution in Poles and Russians. An analysis of the distribution of the control region haplotypes did not reveal any specific combinations of unique mtDNA haplotypes and their subclusters that clearly distinguish both Poles and Russians from the neighbouring European populations. The only exception is a novel subcluster U4a within subhaplogroup U4, defined by a diagnostic mutation at nucleotide position 310 in HVS II. This subcluster was found in common predominantly between Poles and Russians (at a frequency of 2.3% and 2.0%, respectively) and may therefore have a central-eastern European origin.

DNA, Mitochondrial↗
PubMed2000

Experimental pancreatitis induced by synthetic prooxidant tert-butyl hydroperoxide.

The purpose of this study was to verify whether injection of tert-butyl hydroperoxide (Bu(t)OOH, a well-known prooxidant agent) into the bile-pancreatic duct can induce acute pancreatitis. A rapid blockade of the secretion was observed in the majority of the animals after 3 hours of observation. After 6 hours, the secretion reached a very low level, significantly different compared with controls. In groups of rats injected with Bu(t)OOH, pancreatic weight gain was observed compared with the rats injected with physiologic saline. Histology of pancreata removed 3 hours after injection of Bu(t)OOH showed acinar cell vacuolization, interstitial edema, focal necrosis of pancreatic acini, fat-tissue necrosis, and leukocyte infiltration of the organ. These changes were considerably greater after the 6-hour observation period. Electron-microscopic inspection revealed profound morphologic changes 3 hours after Bu(t)OOH injection. The control rats receiving physiologic saline alone had well-preserved pancreatic tissue structure. In conclusion, injection of the prooxidant agent, tert-butyl hydroperoxide, into common bile-pancreatic duct induces acute necrotizing pancreatitis, which indicates the crucial role of free radical reactions in pathogenesis of this disease.

Animals↗
PubMed1999

Population genetics of the STRs vWA, D3S1358 and FGA in the Pomerania-Kujawy region of Poland.

This paper presents the results of a Polish population study (n = 210) for the three STR loci vWA, D3S1358 and FGA analysed using the multiplex PCR system AmpflSTR Blue. The allele distributions were in accordance with Hardy-Weinberg expectations. The combined mean exclusion chance, mean paternity index and power of discrimination for the three loci were MEC = 0.96055, MPI = 127.1295 and PD = 0. 99986. This demonstrates that these systems are valuable tools for forensic identification and paternity testing.

Alleles↗
PubMed1998

Screening of a highly polymorphic microsatellite for microheterogeneity in human identification.

Single-strand conformation polymorphism (SSCP) analysis combined with automated laser fluorescence detection is proposed as a comprehensive, rapid and sensitive method for screening sequence variation of the human beta-actin-related pseudogene (HUMACTBP2). Eleven sequenced alleles representing each type of known sequence variant of HUMACTBP2 locus were studied. Allelic variants of the same size but different sequence structures are easily resolved on the basis of their secondary conformation. Fifty ACTBP2 amplification products previously typed on a denaturing gel were repeatedly examined to determine the utility of SSCP analysis in terms of ease of interpretation and reproduction capabilities of the conformational patterns. Eleven sequenced ACTBP2 allelic variants were used as external conformation standards in polymerase chain reaction (PCR)-SSCP subtyping. This enabled identification of polymorphism in a particular length variant and therefore consistent discrimination between heterozygous samples appeared identical on denaturing gels. Of five "homozygous" samples, one was shown to be heterozygous for two distinct alleles of the same size but different sequences. Thus, the method provides a unique possibility for detecting false homozygotes. The technique complements both denaturing gel electrophoresis and DNA sequencing in studies on the overall variability of the ACTBP2 locus.

Actins↗
PubMed1998

Inhibitory effect of free radicals derived from organic hydroperoxide on progesterone synthesis in human term placental mitochondria.

Different natural and synthetic organic hydroperoxides have been found to stimulate TBARS formation in human term placental mitochondria. The levels of TBARS were lower than arising from NADPH-dependent lipid peroxidation. BHT, Mn2+ and DMPO counteracted TBARS formation in the presence of cumene hydroperoxide implicating involvement of free radicals in this process. On the other hand superoxide dismutase, catalase and EDTA while being inhibitory in NADPH-dependent lipid peroxidation did not inhibit cumene hydroperoxide-dependent TBARS formation. Amphenone B and SKF-525A, inhibitors of cytochrome P-450, strongly inhibit both NADPH- and cumene hydroperoxide-dependent lipid peroxidation. These data provide evidence that cytochrome P-450SCC is involved in both these processes. However NADPH-dependent lipid peroxidation and the cumene hydroperoxide have been found to inactivate placental mitochondrial cytochrome P-450SCC. The presence of cumene hydroperoxide resulted in a more rapid inactivation of cytochrome P-450SCC and consequently inhibited NADPH-dependent lipid peroxidation. It has been observed for the first time that progesterone biosynthesis can be inhibited by cumene hydroperoxide. Protective effect of Mn2+ and DMPO on progesterone biosynthesis indicates the importance of free radicals as transient products of cytochrome P-450SCC-dependent cumene hydroperoxide metabolism. In contrast to progesterone formation from cholesterol, the conversion of pregnenolone to progesterone was not affected by cumene hydroperoxide. This suggests that inhibition of progesterone synthesis from cholesterol by hydroperoxide may be ascribed to its effect on the desmolase activity of cytochrome P-450SCC in placental mitochondria. On the basis of the results obtained, we propose that the inhibition of progesterone biosynthesis by naturally occurring hydroperoxides may contribute to the development of preeclampsia.

Benzene Derivatives↗
PubMed1998

[Carbonyl groups content on the basis of protein peroxidation analysis with total antioxidant status in blood of children with cancers].

Toxic oxygen free radicals have been implicated as important pathologic mediators in carcinogenesis. Several reports have found antioxidants and enzymes related to the antioxidants function at increased or decreased levels in blood of patients with cancers. In previous publications we observed that antioxidant barrier can be different in healthy children and children with cancers. This time we were looking for a stable marker of damaging effect of free radicals reactions in association with antioxidant barrier in blood. Carbonyl group level in proteins has been introduced as a good marker of oxidative stress damage. For this study we selected 60 children at the age of 3 to 16, who had been diagnosed as suffering from cancers: malignant (m) bone tumors (t) (n = 25), m. brain t. (n = 20), lymphoma malignum (n = 5), m. liver t. (n = 5) and m. germ cell t. (n = 5). The control group consisted of 40 age-matched healthy children (22 boys and 18 girls). We investigated the concentration of carbonyl groups (CG) in serum spectrofotometrically, according to the method of Levine. Plasma total antioxidant status (TAS) was estimated colorometrically with radical cation ABTS (2,2'-Azino di-[3-ethylbenzthiazoline sulphonatel]), erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were assessed according to the method of Paglia & Valentine and Minami & Yoshikawa respectively (Kits of Randox Laboratories Ltd.). In this study the content of CG in plasma proteins has shown a significant increase (1.60 +/- 0.77 vs 0.78 +/- 0.15 nmol/mg protein, p < 0.001) and erythrocyte GSH-Px activity has shown a significant decrease (16.3 +/- 7.9 vs 25.1 +/- 15.8 U/gHb, p < 0.02) in children with malignant tumors. No differences were observed in SOD activity and TAS between sick and healthy children. A possible interpretation of this data suggests an inadequate antioxidants' protection in children with cancers. The relationship between the oxidative damage and carcinogenesis requires further investigations.

Adolescent↗
PubMed1997

Novel BRCA1 mutations and more frequent intron-20 alteration found among 236 women from Western Poland.

Three different novel BRCA1 mutations, five independent cases of the same 12 bp insertion-duplication in intron-20 and two novel rare BRCA1 sequence variants were identified among 122 Polish women with positive, in most cases moderate family history of breast and/or ovarian cancer, 80 controls and 34 unselected breast cancer tissue specimens. All mutations and variants were germline. The 4153 delA frameshift mutation, the Tyr105Cys missense mutation and two cases of the alteration in intron-20 were found in the group of healthy women with positive family history. Two other cases of the intronic insertion were found in unselected controls. Their carriers had no family history of breast or ovarian cancer but other cancers occurred in their families. The 1782 Trp/STOP nonsense mutation and one case of the insertion in intron-20 were first found in tissue specimens of breast cancer patient and breast/ovarian cancer patient, respectively. Their carriers also had no family history of breast or ovarian cancer. The distribution of the insertion in intron-20 in analysed groups and results of RT-PCR experiments suggest a less prominent role for this variant considered earlier a splicing mutation. This study shows also, that more population-oriented research is needed, involving women with less profound or even no family history of breast and ovarian cancer, to better understand the role and significance of different BRCA1 variants and mutations.

Adolescent↗
PubMed1997

Optimization of a hexaplex DNA amplification from short tandem repeat and amelogenin loci.

An automated DNA profiling system based on the multiplex amplification of highly polymorphic short tandem repeat (STR) markers and the amelogenin locus was developed. Five STR loci with nonoverlapping allele size ranges have been utilized in the multiplex amplifications, including HUMD1S103, HUMTH01, HUMD21S11, HUMD18S51, and HUMFIBRA. One primer for each locus was labeled with a fluorescent dye (fluorescein) which allows detection on the single wavelength ALF DNA Sequencer (Pharmacia Biotech). As part of the detailed evaluation of the suitability of the hexaplex system for routine forensic use, the effect of variation in amplification parameters on the efficiency of the system was examined. Polymerase chain reaction amplification conditions were optimized to provide specific, robust amplification of forensic samples.

Autoanalysis↗
PubMed1997

[Modification of proteins in the course of oxidative stress in acute experimental pancreatitis].

This study aimed to investigate the protein peroxidation process in cerulein induced acute pancreatitis. Eighteen rats were divided into three equal groups: group 1 acted as control rats had intraperitoneal injection of 0.9% NaCl, in group 2 and 3 rats had injection of cerulein 40 micrograms kg-1 for 3 or 6h of induction period respectively. Protein carbonyls which reflect peroxidative damage were found to be increased after 3h up to 2.53 +/- 0.49 comparing to 1.05 +/- 0.17 in control group and returned to control level 0.95 +/- 0.04 after 6h. These data suggest that during acute pancreatitis free radicals may play an essential role in protein damage. Decrease in protein carbonyls content after 6h suggests an elevated proteolysis of oxidatively damaged proteins.

Acute Disease↗
PubMed1996

[Angiogenesis and its clinical significance].

This study collects past and recent data about neovascularization process and angiogenic factors. Development of the collateral circulation in the heart in response to gradual and progressive coronary artery occlusion was described. Pharmaceutical and surgical methods of angiogenesis induction was discussed. Importance of angiogenic process in many both physiological and pathological situations was noticed. It was pointed out that discovery and cloning of angiogenic cytokines maybe very useful in future treatment.

Animals↗
PubMed1995

Protective effect of 4-hydroxy-TEMPO, a low molecular weight superoxide dismutase mimic, on free radical toxicity in experimental pancreatitis.

Rats develop acute pancreatitis when infused iv for 3 h with cerulein (10 micrograms/kg/h). Autopsies of the pancreas seen by light microscope show interstitial edema, acinar cells vacuolization, and leukocyte margination in pancreatic capillaries; under electron microscope, severe damage concerning mitochondrial and zymogen granules structures are apparent. Particularly, swelling of the mitochondria and disruption of mitochondrial cristae was observed as well as formation of large vacuoles arising from zymogen granules and liposome fusion. A significant increase of lipid hydroperoxide level in the pancreatic tissue was observed. The purpose of this study was to evaluate the effect of 4-hydroxy-TEMPO--a low-mol-wt superoxide dismutase mimic--in a rat cerulein model of acute pancreatitis, with the expectation that free radical mediated hydroperoxide formation and tissue damage may be reduced significantly. Twenty-one male Wistar rats were divided into three groups: Group 1 (n = 5) served as a control and was infused iv for 3 h with physiologic saline; Group 2 (n = 8) was infused i.v. for 3 h with cerulein 10 micrograms/kg/h; and Group 3 (n = 8) infused i.v. both with cerulein and 4-hydroxy-TEMPO 22.6 mg/kg/h. Pancreatic tissue damage was quantified by measuring lipid hydroperoxide (LOOH) level, the weight of the organ, and by light and electron microscopic examination. 4-hydroxy-TEMPO penetration across cellular membrane barriers was quantified by ESR spectrometric measurements of 4-hydroxy-TEMPO concentration in pancreatic tissue samples and pancreatic juice as well. Administering 4-hydroxy-TEMPO to rats resulted in preventing both lipid hydroperoxide formation and severe morphological damage. 4-hydroxy-TEMPO crossed cellular membrane barriers and was excreted to pancreatic juice. Infusion of 4-hydroxy-TEMPO appears to prevent pancreatic injury caused by free radicals in experimental cerulein pancreatitis.

Acute Disease↗