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Biomedical subjects

J Sobczak

Publications and source records attributed to J Sobczak.

16 recordsLinked to original sources
PubMed2001

Molecular mechanism of hydrogen peroxide conversion and activation by Cu(II)-amikacin complexes.

The interactions between Cu(II)-amikacin complexes [Cu(II)-Ami] and hydrogen peroxide were studied by spectroscopy (EPR, UV-vis, CD, XAS) and cyclic voltammetry. A monomer-dimer equilibrium was detected at complex concentrations above 5 mM (log K(dim) = 1.84 +/- 0.03). The dimeric complex undergoes easy, although irreversible oxidation (ca. 0.5-0.6 V) to a Cu(III) species on platinum electrode. However, the monomeric complexes are able to catalyze hydrogen peroxide disproportionation reaction at pH 7.4 in a multistep process, mediated by hydroxyl radicals and involving both Cu(I)/Cu(II) and Cu(II)/Cu(III) redox pairs.

Amikacin↗
PubMed1998

Cyclin A2 and c-myc mRNA expression in ethinyl estradiol induced liver proliferation.

The time-course of c-myc and cyclin A2 mRNA expression was determined in the liver of male Sprague-Dawley rats during transient liver cell proliferation induced by a single dose of ethinyl estradiol (EE), and was compared to that during liver regeneration following two-thirds hepatectomy (PH). Cell proliferation was assessed in terms of 5'-bromodeoxyuridine (BrdU) labeling. EE administration and PH both increased BrdU labeling between 18 and 48 h, with peak values at 18 and 24 h. An early (2 h) increase in BrdU labeling was observed after EE but not PH. Maximal increases in cyclin A2 mRNA levels and BrdU labeling coincided after both EE and PH, and cyclin A2 mRNA expression was proportional to the intensity of the proliferative response. In contrast, the degree of c-myc mRNA expression was similar after EE administration and PH, but the time course was different: c-myc gene expression rose concomitantly with DNA replication after EE, while after PH it increased during the prereplicative phase. This indicates that the pattern of c-myc gene expression in the liver is strongly related to the type of proliferative response.

Animals↗
PubMed1997

Patient autonomy and the euthanasia debate.

For people with terminal illnesses, advance directives can play a significant role in allowing people to express their views about care when physically unable to do so. There is concern that pressure may be put on vulnerable people to make an advance directive. The right to die must be exercised within the bounds of patient autonomy so that the individual plans the end of life with the help of an advance directive.

Ethics, Nursing↗
PubMed1992

Comparison of biochemical properties of DNA-topoisomerase I from normal and regenerating liver.

Biochemical properties of topoisomerase I from normal and regenerating rat liver were analysed using crude or fractionated nuclear extracts. We could not detect significative change in topoisomerase I content or activity (magnesium stimulation and inhibition by ATP) during the course of liver regeneration. Topoisomerase I can be resolved into two species of 97 kDa and 100 kDa, with the same pI of 8.2-8.6 as shown by two dimensional gel electrophoresis. The two polypeptides contained a non-phosphorylated precursor and others forms with variable degrees of phosphorylation. In-vitro dephosphorylation with alkaline phosphatase leads to the disappearance of the phosphorylated forms and inactivation of the enzyme. The affinity of topoisomerase I for chromatin (measured by salt elution) differs markedly between normal and regenerating liver: nearly 50% of topoisomerase I remained bound to the chromatin from normal liver at 250 mM NaCl whereas it was completely eluted from 24-h-regenerating-liver nuclei. The biological significance of these results is discussed.

Adenosine Triphosphate↗
PubMed1992

Cyclin A is required in S phase in normal epithelial cells.

We have investigated cyclin A expression in a primary culture of normal rat hepatocytes and during rat liver regeneration after partial hepatectomy. In both cases, cyclin A mRNA and protein accumulate as the cells enter S phase. To investigate the potential implication of cyclin A accumulation at S phase, we microinjected anti-sense DNA constructs for cyclin A, resulting in effective inhibition of S phase entry. These effects were specific for cyclin A since anti-sense cyclin B construct had no similar effects. These results therefore, obtained in normal epithelial cells, indicate that cyclin A is involved in S phase and thus should not be only considered as a mitotic cyclin.

Animals↗
PubMed1989

Gene expression in regenerating liver in relation to cell proliferation and stress.

When hepatocyte proliferation is stimulated in the liver by partial hepatectomy, messenger RNAs coding for fibrinogen, actin, c-myc and topoisomerase I are rapidly accumulated. We distinguish an early phase of accumulation (0-3 h after partial hepatectomy) which is also observed after a sham operation for the four genes, and during inflammation produced by Freund's adjuvant in the case of fibrinogen and c-myc genes. The hepatic response to inflammation appears therefore to mimic events characteristic of the G0/G1 transition, such as the accumulation of the c-myc mRNA. The late phase of mRNA accumulation (beyond 3 h after partial hepatectomy) is typical of liver regeneration. The level of c-myc mRNA is transiently increased (20-fold over normal) 20 h after partial hepatectomy, that is, at the time of DNA synthesis. Topoisomerase-I mRNA level increases between 3 and 24 h after partial hepatectomy (5-10-fold over normal). These results suggest that accumulation of c-myc and topoisomerase-I mRNAs is associated with DNA replication in regenerating liver.

Actins↗
PubMed1989

c-myc and c-fos gene regulation during mouse liver regeneration.

We have examined the expression of c-myc and c-fos proto-oncogenes in regenerating mouse liver, in order to analyse the relative contributions of transcriptional and post-transcriptional regulations in vivo. We show that c-myc and c-fos transcription is induced after partial hepatectomy, and involves common mechanisms. A strong block to transcriptional elongation exists in normal liver, within the first exon of c-myc gene. This block is only slightly relieved during liver regeneration, although transcriptional initiation is transiently increased (4-6 fold). In contrast, transcription initiation of c-fos is induced while the transcriptional block within the first exon of the gene is almost completely abolished. The steady-state levels of both transcripts increased to high levels (50-100 fold) within 2-6 h after partial hepatectomy, and were maintained for at least 40 h in the case of c-myc. We conclude that post-transcriptional control mechanisms are largely responsible for the dramatic induction of c-myc mRNA in regenerating liver, while c-fos mRNA accumulation is the result of both an increased initiation and a relief of a transcriptional block to elongation. Induction of both genes in vivo with cycloheximide argues in favor of negative trans-acting proteins which regulate initiation and elongation of transcription.

Animals↗
PubMed1988

Effect of histone H1, poly(ethyleneglycol) and DNA concentration on intermolecular and intramolecular ligation by T4 DNA ligase.

The efficiency of ligation of linear DNA and the relative amounts of intramolecular versus intermolecular ligation may be triggered by a number of additive agents. The results show that it is possible to mimic the effect of poly(ethyleneglycol) 6000 by simply increasing DNA concentration about 15-fold: both the rate and the extent of the reaction are greatly enhanced, and intermolecular ligation is largely favored. However, in this case the stimulation by salts, which occurs in poly(ethyleneglycol) solutions, is not observed; we suggest that salts enhance the hydrophobic interactions between ligase and DNA that take place in the presence of poly(ethyleneglycol). We also show that histone H1, which is involved in the formation of chromatin fibers, is able to stimulate intermolecular ligation by T4 ligase. This effect is more specific than a simple neutralisation of the phosphate groups of the DNA by positive charges of the histone; it still occurs at 125 mM NaCl and in the presence of the four core histones. The implications of the finding concerning the mode of action of histone H1 on DNA are discussed.

DNA Ligases↗
PubMed1987

Molecular cloning of mRNA sequences transiently induced during rat liver regeneration.

In order to isolate genes which are induced during liver regeneration, we have constructed a cDNA library from 16-h-regenerating liver poly(A)+ RNA. By computer analysis of autoradiograms produced by differential plaque hybridization with cDNA from normal or 16-h-regenerating liver, we have isolated several recombinant clones representing sequences transiently increased during liver regeneration. Three of these were further characterized: the level of the corresponding mRNAs increase rapidly after partial hepatectomy, before the onset of DNA synthesis. Two clones were identified as fibrinogen clones. It is speculated that alpha-fibrinogen may be involved in the growth process, or in its regulation.

Animals↗
PubMed1984

Rat liver HMG1: a physiological nucleosome assembly factor.

Incubation of rat liver single-stranded DNA-binding protein HMG1 with the four core histones at 0.15 M NaCl favors histone association primarily into tetramers and, to a lesser extent, into octamers. The assembly of pre-formed histone-HMG1 complexes with DNA yields nucleosome-like subunits which satisfy most of the criteria defining native core particles: (i) the circular DNA extracted from the complexes is supercoiled indicating that the initially relaxed DNA acquired superhelical turns during complex formation in the presence of topoisomerase I; (ii) the digestion of the complexes with micrococcal nuclease yields a DNA fragment of approximately 140 bp in length; (iii) electron microscopy of the reconstituted complexes shows a beaded structure with the DNA wrapped around the histone cores, leading to a reduction in the contour length of the genome compared with free DNA. Moreover, in the presence of HMG1, nucleosome assembly occurs rapidly at 0.15 M NaCl. Therefore, in addition to its DNA-binding properties, HMG1 mediates the assembly of nucleosomes in vitro under conditions of physiological ionic strength. The possible involvement of these properties in the DNA replication process is discussed.

Animals↗
PubMedDate not supplied

Molecular biology of liver regeneration.

Liver regeneration is a good system for studying cell proliferation in an in vivo, physiologically controlled situation. Various hepatotrophic factors, neuromediators, hormones and growth factors, presumably acting in synergy, seem necessary to induce the switch from quiescence to proliferation. As a consequence of this activation, a number of changes occurs in the hepatocyte: modifications of the plasma membrane proteins; metabolic changes such as variations in albumin and fibrinogen concentrations, and induction of the acute phase proteins; induction of several specific mRNAs; variations in cAMP concentrations, and consequently in the activity of protein kinases and several other enzymes; modifications in chromosomal proteins; induction of proteins involved in DNA replication. A model has been constructed which is more a basis for reflexion than a theoretical model. It takes into account the possible connections between the different molecular events cited above. It is hypothesized that DNA replication is at least partly uncoupled from mitosis, and that the initial events of the proliferative response may be triggered by nutritional elements.

Animals↗
PubMedDate not supplied

Music and movement to exercise older people.

While life expectancy is increasing, research suggests that there has not been a corresponding improvement in health in older age. This article considers the role of exercise in promoting healthy ageing and describes a nurse-led exercise programme for older people.

Aged↗