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Biomedical subjects

J Dziuba

Publications and source records attributed to J Dziuba.

15 recordsLinked to original sources

Breast cancer predisposing alleles in Poland.

Mutant alleles of several genes in the DNA repair pathway have been found to predispose women to breast cancer. From a public health perspective, the importance of a given allele in a population is determined by the frequency of the allele and by the relative risk of breast cancer that it confers. In Poland founder alleles of the BRCA1, CHEK2 and NBS1 genes have been associated with an increased risk of breast cancer, but the relative contribution of each of these alleles to the overall breast cancer burden has not yet been determined. We screened 2012 unselected cases of breast cancer and 4000 population controls for 7 different mutations in these genes. Overall, a mutation was found in 12% of the cases and in 6% of the controls. Mutations in BRCA1 and CHEK2 contributed in approximately equal measure to the burden of breast cancer in Poland. A BRCA1 mutation was present in 3% of the cases. The missense BRCA1 mutation C61G was associated with a higher odds ratio for breast cancer (OR=15) than were either of the truncating BRCA1 mutations 4153delA (OR=2.0) and 5382insC (OR=6.2). In contrast, a higher odds ratio was seen for truncating CHEK2 mutations (OR=2.1) than for the missense mutation I157T (OR=1.4). This study suggests that cancer risks may be specific for particular alleles of a susceptibility gene and that these different risks should be taken into account by genetic counselors.

Adult↗

The effect of glycosylation on emulsifying and structural properties of bovine beta-casein.

A number of attempts have been made to improve the functional properties of milk proteins by chemical modifications. One of such modifications is glycosylation which was carried out to determine the effect of covalent binding of glucose molecules to beta-casein (beta CN) on its emulsifying properties. It was found that up to six molecules of glucose were bound to one molecule of beta CN. Glycosylated beta CN produced smaller emulsion droplets than the intact beta CN. Increases in emulsion-forming and -stabilizing properties were observed. A prerequisite of proteins to form emulsions is their adsorption onto oil/water interface. Therefore the secondary structure of intact and glycosylated beta CN, both in solution and adsorbed onto a hydrophobic teflon/water interface also were studied by far-ultra violet circular dichroism (CD). It appeared, that after glycosylation the degree of helicity of intact beta CN decreased and the incorporation of glucose moieties most likely resulted in a type beta-turn formation after adsorption onto the interface.

Adsorption↗

Dephosphorylation-induced structural changes in beta-casein and its amphiphilic fragment in relation to emulsion properties.

To promote the understanding of the relationship between emulsifying and molecular properties of proteins/peptides, intact beta-casein (betaCN) and its amphipathic fragment, i.e., betaCN (1-105/107) were dephosphorylated. Dephosphorylation was found not to change significantly their emulsifying properties. Since it is known that the structure of proteins can change upon adsorption onto an interface, the secondary structure of intact beta-casein, its amphipathic fragment, and their dephosphorylated forms, both in solution and after adsorption onto a hydrophobic teflon/water interface, were studied by far-UV circular dichroism spectroscopy. An increased content of secondary structure, especially alpha-helix, was found for all samples after adsorption onto teflon. Dephosphorylation increased the helix-forming propensity, especially for amphipathic fragment of beta-casein. No influence of the secondary structure properties on the emulsion-forming and -stabilizing properties was observed, but a relationship between the maximum surface load and the emulsion-stabilizing properties was found.

Caseins↗

Database of biologically active peptide sequences.

Proteins are sources of many peptides with diverse biological activity. Such peptides are considered as valuable components of foods with desired and designed biological activity. Two strategies are currently recommended for research in the area of biological activity of food protein fragments. The first strategy covers investigations on products of enzymic hydrolysis of proteins. The second one is synthesis of peptides identical with protein fragments and investigations using these peptides. It is possible to predict biological activity of protein fragments using sequence alignments between proteins and biologically active peptides from database. Our database contains currently 527 sequences of bioactive peptides with antihypertensive, opioid, immunomodulating and other activities. The sequence alignments can give information about localization of biologically active fragments in protein chain, but not about possibilities of enzymic release of such fragments. The information is thus equivalent with this obtained using synthetic peptides identical with protein fragments. Possibilities offered by the database are discussed using wheat alpha/beta-gliadin, bovine beta-lactoglobulin and bovine beta-casein (including influence of genetic polymorphism and genetic engineering on amino acid sequences) as examples.

Animals↗

Distinct ICAM-1 forms and expression pathways in synovial microvascular endothelial cells.

Human synovial endothelial cell (HSE) intracellular adhesion molecule-1 (ICAM-1) is upregulated maximally by synergy of tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma). Such synergy is not as pronounced in human umbilical vein endothelium (HUVE). ICAM surface staining and ELISA detection reflected similar levels on HUVE and HSE cells, yet mRNA levels were much higher in HSE cells in response to TNF alpha/IFN gamma. To correlate protein and mRNA levels of ICAM-1, both cell types were permeabilized and stained with a monoclonal antibody against ICAM-1. HSE cells displayed a distinct vesicular cytoplasmic staining for ICAM while HUVE cells were devoid of such stained vesicles upon staining with the antibody. ICAM-1 immunostaining of HSE cytoplasmic vesicles appeared enhanced in cells treated with TNF alpha/IFN gamma and monensin, an endosomal processing inhibitor. Monensin inhibited HSE cell surface expression of ICAM-1 routinely up to 70%, while HUVE cell expression was unaffected. In addition, monensin also inhibited soluble ICAM-1 release from HSE cells while not effecting HUVE cells. Immunoprecipitation of ICAM-1 followed by gel electrophoresis indicated that HUVE and HSE cell ICAMs are expressed in cell-specific forms. These results define distinct forms and distinct secretory pathways for ICAM-1 in HSE cells and HUVE cells that indicate functional differences between these human endothelia.

Cells, Cultured↗

Some physico-chemical properties and structural changes of bovine beta-casein upon glycation.

The studies on casein structure modification contribute to better understanding of the role of nonamino acid components in forming casein complexes and improving ways of protein functionality. The objective of the experiments was to explain the influence of bovine milk casein glycation on some physico-chemical properties and structural changes. From the the analysis of glycation rate curve the reaction of the first order range can be assumed during the first 24 h, turning to a mixed type afterwards. The isoelectric point and molecular weight of beta-casein increased after glycation and the electrophoretic mobility was slightly modified. The structural changes were also confirmed by different absorption spectra in UV and a better heat stability of the modified beta-casein. The findings showed higher solubility with modified beta-casein. The glycation caused changes in beta-casein, modifying its susceptibility to the trypsin hydrolysis.

Amino Acids↗

[The effect of lithium chloride on the rat behavior after short-term oligemic hypoxia].

The experiments were carried out on male Wistar rats. The influence of brain oligemic hypoxia and lithium chloride (LiCl) on some behavioural parameters was investigated. Reduction of brain blood supply was performed by surgical clamping of both carotid arteries for 60 min in general anaesthesia induced by brietal (Methoxitone sodium, 10 mg/kg i.p.). Control animals had their vessels separated, but not clamped (sham operated). 6 days after surgery animals received LiCl (2.5 mEq/kg i.p.). Behavioral experiments were performed 24 h and 7 days after lithium administration. Experimental groups consisted of 12 animals. It was found that oligemic hypoxia reduced inconsiderably spontaneous locomotor and exploratory activity in rats. Similar influence of LiCl was observed. But LiCl administered to animals after oligemic hypoxia prevented them against locomotor and exploratory impairment. In addition, LiCl strongly enhanced amphetamine-induced hyperactivity and diminished haloperidol-induced catalepsy in hypoxic animals. These effects were not observed in sham operated animals. The above results could be connected with antidepressive action of LiCl and the model of moderate oligemic hypoxia used in present work could be a useful model for investigation of new antidepressive compounds.

Amphetamine↗

Cytotoxic effects of singlet oxygen.

The toxic effects of gas-phase singlet oxygen, 1O2, on the ciliated respiratory epithelium of hamster trachea have been demonstrated. Tracheal explants treated with 1O2 showed a dose-dependent decrease in cilia beating frequency and focal ciliostasis. A statistically significant decrease in ciliary activity occurred at 1O2 concentrations as low as 154 ppb after a 2-hr exposure. Cytological alterations in the mucociliary epithelium were observed in explants exposed to 235 ppb 1O2 or greater. When cytotoxic effects were related to the time of exposure to 1O2, maximum effects occurred after a 4-hr exposure. In vitro recovery studies indicate that ciliary activity returned to normal between 4 and 8 hr after exposure.

Animals↗