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Biomedical subjects

J Lunec

Publications and source records attributed to J Lunec.

At least 199 records · Page 11Linked to original sources
PubMed1985

The determination of dehydroascorbic acid and ascorbic acid in the serum and synovial fluid of patients with rheumatoid arthritis (RA).

Using a novel high performance liquid chromatography (HPLC) determination of ascorbic acid and dehydroascorbic acid, we have measured the relative amounts of ascorbate and dehydroascorbate in 20 normal controls and in paired sera and synovial fluid from 13 patients with rheumatoid arthritis (RA). In complete contrast to previous published findings we were able to detect dehydroascorbate in normal human sera (12.0 +/- 3.7 mumol/l), while the mean and range of ascorbate measured in normals was 69.6 +/- 20.6 mumol/l. These findings were completely reversed in rheumatoid sera (21.8 +/- 8.6 mumol/l and 5.1 +/- 5.0 mumol/l for dehydroascorbate and ascorbic acid respectively). In several rheumatoid sera no ascorbate could be detected. In paired synovial fluid and serum samples, there was always more dehydroascorbate detected in synovial fluids than in the corresponding sera (p less than 0.01). The data suggests that the reduced level of ascorbate and increased level of dehydroascorbate may be a reflection of the increased antioxidant and free-radical scavenging activity of the vitamin in RA, especially within the inflamed joint.

Adult↗
PubMed1985

A possible role for ferritin during inflammation.

Inflammation induces the hepatic synthesis of the iron storage protein (apo)ferritin, which is released into the circulation, and behaves as an acute phase protein. The biological significance of the extracellular rise in serum (apo)ferritin is unknown. We have observed that (apo)ferritin will stimulate superoxide production from neutrophils in the presence of cytochalasin B across a physiologically appropriate concentration range. We therefore propose that extracellular ferritin has an important role in host defence against bacteraemia by stimulating oxidative metabolism.

Animals↗
PubMed1985

Cerebral and ocular toxicity induced by desferrioxamine.

Seven patients with rheumatoid disease were given the iron-chelating drug desferrioxamine (DFX) to evaluate its possible anti-inflammatory effects. Two of these patients, who also received the anti-emetic prochlorperazine, lost consciousness for 48-72 h and then fully recovered. Electroencephalography showed abnormalities of the type associated with metabolic disturbance. One of these patients showed pyramidal features and subsequently developed an optic neuropathy and pigmentary retinopathy. Analysis of his cerebrospinal fluid showed a decrease in loosely-bound (catalytic) iron and increase in loosely-bound (catalytic) copper, total iron and products of lipid peroxidation, with values approaching normal as the symptoms resolved. Subsequent in vivo/vitro studies clearly demonstrated that the neurological effects were due to a synergistic action of desferrioxamine and prochlorperazine, probably resulting in exceptional fluxes of intra/extra cellular iron/copper disturbing noradrenergic and serotonergic systems. Two other patients who did not receive prochlorperazine, developed retinal problems which later improved, one after only 15 g of desferrioxamine. Our observations suggest a new model for metabolic encephalopathy studies and provide insight into the mechanisms of pigmentary retinopathy.

Adult↗
PubMed1984

Action of free radical generating systems upon the biological and immunological properties of caeruloplasmin.

Exposure of human caeruloplasmin, an acute phase protein with antioxidant properties, to a mixture of xanthine/hypoxanthine and xanthine oxidase as a source of reactive oxygen intermediates decreased its ferroxidase and ascorbate oxidase activities and its ability to inhibit lipid peroxidation. Immunological reactivity was also altered. Exposure to hydrogen peroxide mimicked these effects. Exposure to low-intensity u.v. irradiation depressed caeruloplasmin's ability to inhibit iron-catalysed hyaluronic acid degradation. The results may explain the mechanism of the observed inactivation of caeruloplasmin within human rheumatoid synovial fluid.

Ascorbate Oxidase↗
PubMed1984

Introductory review: involvement of ADP-ribosylation in cellular recovery from some forms of DNA damage.

There is substantial evidence that ADP-ribosylation is stimulated in response to DNA strand breaks produced directly by a damaging agent or during excision repair processes. The report of a reduced stimulation of ADPRT activity in irradiated ataxia telangiectasia cells has recently stimulated a wide interest in the role of ADP-ribosylation in cellular radiation response. The resulting studies, some of which are presented at this conference, demonstrate that cellular recovery from radiation damage can be significantly impaired if ADP-ribosylation is inhibited to a sufficiently low level. The implication is that the repair of DNA lesions is affected. This review summarizes the involvement of the enzyme ADPRT and the extent of ADP-ribosylation in the repair of DNA damage and of cellular recovery.

Adenosine Diphosphate Ribose↗
PubMed1984

Post-irradiation sensitization with the ADP-ribosyltransferase inhibitor 3-acetamidobenzamide.

In recent years several lines of evidence have indicated that nuclear ADP-ribosyltransferase (ADPRT) activity is involved in DNA repair, although the requirement of ADPRT activity for cell survival has only been demonstrated in certain cases. We have investigated further the possible role of ADP-ribosylation in the response of cells to ionizing radiation, using 3-acetamidobenzamide (3-AAB), a highly effective inhibitor of ADPRT. With this compound we have demonstrated that marked enhancement of cell killing is observed if ADP-ribosylation is inhibited to a sufficient extent during the post-irradiation repair period, using concentrations of 3-AAB which are not toxic towards unirradiated cells. The critical period within which the inhibitor was effective was the first 90 min post-irradiation, and the half life of the recoverable radiation damage involved was estimated as approximately 20 min. Treatment with 3-AAB slowed the rate at which DNA strand breaks were repaired but did not prevent the ultimate repair of breaks, within the limits of resolution of the alkaline unwinding method used to determine DNA strand breakage. Although the majority of breaks were ultimately repaired, the frequency of radiation-induced sister chromatid exchanges and chromosome aberrations was increased, indicating that more genomic rearrangement had taken place, possibly as a consequence of the persistence of breaks when ADPRT activity was inhibited by 3-AAB during the post-irradiation repair period. It is suggested that the increased frequency of transposition and recombination which these observations reflect is likely to be associated with an increased risk of lethal mutations, some possibly involving chromosomal aberrations.

Adenosine Diphosphate Ribose↗
PubMed1984

Differences in repair in heterogeneous cell populations in vivo and in vitro following high LET irradiation (neutrons).

The shape of cell survival curves following X-irradiation when the X-rays were given immediately after neutron irradiation has been examined in two cell lines in vitro (Ehrlich ascites and V79) and in the stem cells of the mouse jejunum. The changes in the shape of the X-ray survival curve following neutron irradiation are different in all the cell systems examined. Some of the changes observed may be associated with a change in the cell profile following neutron irradiation due to the more even cell age killing pattern of neutrons through the cell cycle compared with X-rays. It is unlikely that this can account for all changes in shape observed and it is postulated that some cells following neutron irradiation are more sensitive to X-rays than the unirradiated population or than X-irradiated cells at the same level of survival. This increased sensitivity may be associated with a non-reversible sublethal damage or a saturation of the repair potential caused largely by the alpha or heavy recoil (HR) particles produced by the neutrons in the cell nucleus. The damage is observed when the probability of alpha or HR particles being produced within the cell nucleus, without killing the cell, is high.

Animals↗
PubMed1983

Fluorescence changes in human gamma-globulin induced by free-radical activity.

Low-intensity ultraviolet irradiation was used to generate free-radical activity in lipid-free human gamma-globulin. The changes were monitored by fluorescence spectroscopy and gel filtration chromatography. The pattern and the effect of thiol compounds, free-radical scavengers and antioxidants point to a free-radical-mediated process. Initial energy uptake was probably in the region of aromatic amino acid residues, followed by complex intramolecular rearrangements. Irradiation led to the formation of molecular species and complexes whose fluorescence characteristics were different from those of native gamma-globulin and indistinguishable from those observed in inflammatory exudates.

Free Radicals↗
PubMed1983

Effect of membrane fatty acid changes on the radiation sensitivity of human lymphoid cells.

To test the influence of changes in membrane fatty acid composition on the radiation response of mammalian cells, human LDV cells were cultured in medium containing delipidated serum supplemented with either oleic or linoleic acid. Analysis of lipid extracts of the cells by gas liquid chromatography showed that, after 3 or more days growth in oleic or linoleic acid supplemented media, there were substantial overall increases in the proportion of oleate and linoleate, respectively, in the cellular lipid. Smaller absolute changes were measured in nuclear phospholipid, which was found to be low in unsaturated phospholipid compared to the rest of the cell. Fluorescence polarization measurements using diphenylhexatriene indicated an increased membrane fluidity in cells grown in the presence of excess linoleic acid and to a lesser extent for oleic acid. The clonogenic capacity of the cells after irradiation in air or nitrogen was not altered by any of these membrane compositional changes. The lack of effect on radiation sensitivity, in contrast to that reported for bacteria (E. coli K1060), is consistent with the fact that little or no change was brought about in the nuclear membrane composition, since evidence from partial cell irradiation experiments indicates that the cell nucleus is the sensitive target for cell killing by ionizing radiation. The ability of the cell to maintain a low level of unsaturated phospholipids in its nuclear membrane may be an important general defence mechanism against free radical damage to chromatin mediated by lipid peroxidation.

Cell Division↗
PubMed1983

Post-irradiation inhibition of scheduled DNA synthesis and stimulation of ADP-ribosylation in sensitive and resistant L5178Y murine lymphoma cells.

Post-irradiation changes in DNA synthesis and ADP-ribosyltransferase (ADPRT) activity in L5178YS and L5178YR, radiation sensitive and resistant murine lymphoma cells are described. DNA synthesis was inhibited to a greater extent in L5178YS than in L5178YR cells. The stimulation of ADPRT activity by irradiation was not significantly different between these two cell lines. These observations contribute to other evidence which has failed to confirm a general association of ADP-ribosylation with the DNA synthesis inhibition response. The contrast between the response of L5178Y cells and the corresponding behaviour of ataxia telangiectasia cells and normal human cells indicate that entirely different mechanisms are involved in determining the differences in radiosensitivity in these two systems.

Animals↗
PubMed1983

Heat-induced thermotolerance expressed in the energy metabolism of mammalian cells.

Measurements were made of the effect of heat treatment on ATP levels in control and thermotolerant populations of murine lymphoma (L5178YS) and Ehrlich ascites cells to investigate whether the development of thermotolerance is associated with an increased ability of cells to maintain energy metabolism when challenged with heat treatment. For the L5178YS cells a single heat treatment produced a rapid reduction in ATP levels. However, previously heat treated L5178YS cells showed an increased ability to maintain ATP levels when challenged with a second heat treatment, and this ability to maintain ATP levels varied in a manner which correlated with the appearance and decay of thermotolerance seen in the parallel cell survival studies. In contrast both single and fractionated heat treatments did not reduce ATP levels in Ehrlich ascites cells.

Adenosine Triphosphate↗
PubMed1981

Free-radical mediated aggregation of human gamma-globulin.

Ultra-violet irradiation of human gamma-globulin results in aggregation and the formation of fluorescent products. The fluorescence was inhibited by ascorbate and propyl gallate indicating the release of oxygen-free radicals.

Free Radicals↗
PubMed1981

Free radical oxidation (peroxidation)products in plasma in normal and abnormal pregnancy.

Using recently developed methods for measuring free-radical oxidation products in biological material, plasma extracts were studied in 24 women in the first two trimesters of pregnancy, in 124 women in the third trimester of pregnancy, in 20 women with pre-eclamptic toxaemia (PET), and in a control group. There was a significant progressive rise of two groups of free-radical oxidation products throughout pregnancy and a significantly greater rise in PET. In women whose diastolic blood pressure rose to above 70 mmHg there was a highly significant relation between two groups of free-radical reaction products and blood pressure.

Blood Pressure↗