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Biomedical subjects

J Lunec

Publications and source records attributed to J Lunec.

At least 145 records · Page 8Linked to original sources
PubMed1990

Alpha-melanocyte-stimulating hormone immunoreactivity in melanoma cells.

Using a radioimmunoassay specific for alpha-melanocyte-stimulating hormone (alpha-MSH), significant levels of immunoreactivity were detected in a range of murine and human melanoma cell lines, including a series of ras-transfected melanocytes. The levels found in the melanoma cell lines tested varied, and overall were higher than in non-melanoma cell lines assayed for comparison. Furthermore the highest levels of immunoreactivity measured tended to be in the least differentiated and most metastatic melanoma lines. High performance liquid chromatography showed a peak of immunoreactivity which co-migrated with a desacetyl alpha-MSH standard. Additional unidentified components of immunoreactivity were found, including a high molecular weight form revealed by Sephadex-G50 gel exclusion. These may represent bound alpha-MSH or fragments of the proopiomelanocortin precursor having in common the C-terminus epitope recognised by the antibody. In view of the known effects of alpha-MSH on anchorage independent growth and metastasis of melanoma cells, our findings raise the possibility that MSH peptides may have an autocrine role in the growth and progression of melanoma. However, further characterisation of the immunoreactive species is required to determine whether these represent biologically active forms.

Animals↗
PubMed1990

Free radicals and antioxidant systems in health and disease.

Free radical (FR) mechanisms have both beneficial and deleterious actions in vivo. Intensive scientific interest in FRs over the last 20 years has led to a clearer understanding of their roles and helped to clarify the contribution of our intrinsic defence systems (antioxidants) in limiting FR-induced tissue damage. As more and more conditions are shown to have a FR aetiology it becomes imperative to develop newer therapies to prevent and treat FR-induced disease.

Antioxidants↗
PubMed1989

The human red blood cell glyoxalase system in diabetes mellitus.

Methylglyoxal and other alpha-oxoaldehydes are formed from glycolytic intermediates and may be involved in the development of diabetic microangiopathy. Glyoxalase I and glyoxalase II metabolise methylglyoxal to D-lactic acid, via the intermediate S-D-lactoylglutathione. The activities of the glyoxalase enzymes and the concentrations of methylglyoxal and S-D-lactoylglutathione were measured in erythrocytes of 45 control and 85 diabetic subjects (41 with retinopathy and 44 uncomplicated). The concentration of S-D-lactoylglutathione was increased in diabetic patients vs. controls (21.4 +/- 9.3 vs. 12.4 +/- 4.8 mumol/l, P less than 0.001), as was methylglyoxal (3.6 +/- 2.3 vs. 1.4 +/- 0.2 mumol/l, P less than 0.001). There were no significant differences in the activities of glyoxalase I and glyoxalase II between diabetic patients and controls. For insulin-dependent patients only, those without retinopathy had a higher activity of glyoxalase II than those with retinopathy (P less than 0.05). A group of age- and duration-matched insulin-dependent diabetic patients with retinopathy also had a higher activity of glyoxalase I compared with a group of diabetic patients without retinopathy (P less than 0.025). This study provides evidence for elevated concentrations of oxoaldehydes in diabetes mellitus which might have pathogenic significance.

Adult↗
PubMed1989

The effects of oxygen free radicals on the carbohydrate moiety of IgG.

The CH2-linked glycoform of rheumatoid IgG is abnormal in having a reduced galactose content. This has been postulated to be a synthetic defect due to a decrease in the level of rheumatoid B cell galactosyltransferase. However, more recent work has indicated that agalactosylation may be common to chronic inflammatory diseases. In this work we have investigated the effect of oxygen free radicals (OFRs), which are generated by activated phagocytic cells at inflammatory sites, on the carbohydrate moiety of IgG. Radiolytically generated peroxy (ROO.) and hydroxyl radicals (OH.) but not superoxide anion radicals (O2.-) were found to destroy galactose on IgG. After OH. attack, this was associated with an increase in the availability of N-acetylglucosamine, possibly due to its presence as a terminal residue. These results suggest that the agalactosylation associated with chronic inflammation may not only be synthetic in nature, but may also be a consequence of post-synthetic degradation by OFRs.

Acetylglucosamine↗
PubMed1989

Reactive oxygen species induce antigenic changes in DNA.

Reactive oxygen species (ROS) are released at sites of inflammation during the respiratory burst which accompanies the phagocytic process. Using an in vitro system to simulate this process we have shown that ROS induce antigenic changes in DNA. More specifically, results of experiments using ROS scavengers have shown that hydroxyl radicals produced in close proximity to DNA-bound metal ions play a predominant role. ROS-mediated attack resulted in increased binding of anti-DNA antibodies to the denatured DNA. These changes were detected using IgG, IgA and IgM isotype binding to antibodies in systemic lupus erythematosus sera. Of these the IgA isotype was most discriminating in its detection of hydroxyl radical-induced damage.

Animals↗
PubMed1989

Effects of oxidative stress on some physiochemical properties of caeruloplasmin.

We report the effects of oxidative stress generated by low-intensity u.v. irradiation (366 and 254 nm), dialysis against ascorbate and isolated stimulated neutrophils on some physicochemical properties of caeruloplasmin. Low-intensity u.v. irradiation resulted in a loss of ferroxidase activity and 610 nm absorption, changes previously reported to occur during storage and manipulation of caeruloplasmin. These alterations were found to correspond to aggregation of the protein, induction of visible fluorescence (excitation, 360 nm; emission, 454 nm), changes in c.d. spectra which were indicative of alterations in protein conformation, loss of half-cystine, tryptophan and tyrosine content and loss immunoreactivity. The changes in the far-u.v. c.d. spectrum of caeruloplasmin were more pronounced than those observed for u.v.-irradiated IgG. Similar c.d. changes and induction of fluorescence were observed following dialysis of caeruloplasmin against ascorbate or exposure to stimulated neutrophils. It is concluded that the lability of caeruloplasmin may arise from oxidative modification, in addition to the previously described susceptibility of this protein to proteolysis.

Amino Acids↗
PubMed1989

Hypoxic-reperfusion injury in the inflamed human joint.

A series of experiments showed that, on exercise of the inflamed human knee, intra-articular pressure rises above synovial capillary perfusion pressure, causing intra-articular hypoxia; and that, on cessation of exercise, there is oxidative damage to lipids and IgG within the joint. These findings are consistent with the hypothesis that persistence of synovial inflammation can be due to exercise-induced hypoxic-reperfusion injury mediated by reactive oxygen species.

Adult↗
PubMed1989

Ocular toxicity of desferrioxamine--an example of copper promoted auto-oxidative damage?

Three patients with rheumatoid disease were given the 'iron chelating' drug desferrioxamine (DFX), which also has an appreciable affinity for copper. The drug was injected cautiously, in lower doses than in patients with thalassaemia, and intramuscularly to evaluate its anti-inflammatory effects. Two of the three patients developed ocular abnormalities. One patient, who also received methyldopa, developed severe but reversible visual failure associated with an abnormal electro-oculogram (EOG); another showed reversible depression of the EOG. Analysis of the cerebrospinal fluid (CSF) of this patient showed an increase in phenanthroline detectable (non-caeruloplasmin-bound) copper. Analysis of the CSF of the third patient, who did not develop any clinical or electrophysiological ocular abnormalities, was normal. Haematological assessments indicated that all three patients probably had reduced iron stores. With in-vitro systems DFX was shown to mobilise copper from albumin and to facilitate copper movement across a cell membrane model, a property that was enhanced by methyldopa. Our observations are consistent with the concept that in rheumatoid patients low iron stores may result in binding of copper by DFX and that this may be of central importance in causing the ocular toxicity of DFX.

Aged↗
PubMed1989

Automated enhanced latex agglutination assay for rheumatoid factors in serum.

This improved assay of rheumatoid factors in serum, described here for use with the Baker "Encore" centrifugal analyzer, is efficient, with 250-sample throughput per hour; reproducible, with between-batch CV = 5% and within-batch CV = 2% (mid-assay range); and results correlate well (r = 0.9) with those by other methods. The method is fully quantitative and automated, involves no predilution steps, and can be adapted for use in a wide range of systems. It has a sensitivity of 96% and specificity of 80% in diagnosing rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1988

Oxygen radical induced alterations in polyclonal IgG.

In the sera and synovial fluid of patients with rheumatoid arthritis, part of the IgG fraction is found in an aggregated and fluorescent form. Oxygen-free radicals have been implicated in this denaturation, although the precise radical species responsible is unknown. In this work, oxygen-free radicals generated radiolytically were allowed to attack polyclonal IgG in solution. OH radicals induced aggregation of the monomer and a new fluorescence appeared in the visible region (Ex 360 nm, Em 454 nm). The superoxide radical anion was found to be inert in both these respects, whilst peroxy radicals induced autofluorescence without concomitant aggregation. The results suggest that OH.and/or peroxy radical attack may be an in vivo mechanism for IgG denaturation.

Chromatography, Gel↗
PubMed1988

Clinical biochemical measurements in rheumatology.

Despite 50 years of intensive research in the field of RFs, autoimmunity and chronic inflammation, some of the serological tests used for measuring autoantibodies remain an anachronism. Clinical chemistry has the potential technology to provide the rheumatologist with automated quantitative antibody/antigen measurements. It can also widen the range of tests available for disease monitoring, which would be helpful in the management of the chronic rheumatic diseases. Traditional laboratory tests must be superseded by new developments, derived from fundamental research, if we are to improve the diagnosis and management of the rheumatic diseases.

Acute-Phase Proteins↗
PubMed1988

Structural damage to lymphocyte nuclei by H2O2 or gamma irradiation is dependent on the mechanism of OH. radical production.

Normal human lymphocytes were exposed to OH. radicals produced indirectly by exposure to H2O2 or directly by gamma irradiation. Using a flow cytometry technique to measure changes in nucleoid size, it was found that generation of OH. in each system produced a characteristic relaxation in nuclear supercoiling. Exposure of cells to H2O2 produced a metal-dependent step-wise relaxation in extracted nucleoids, while gamma irradiation induced a gradual dose-dependent increase in nucleoid size. The site-specific metal-dependent changes produced in lymphocytes incubated in H2O2 should also occur in gamma irradiated cells, but the characteristic effects on nuclear supercoiling would not be detected within the background of random DNA damage. The importance of metals in maintaining the supercoiled loop configuration of DNA within the protein matrix suggests that free radical damage at metal locations may be particularly toxic for the cell.

Adult↗
PubMed1988

The fluorescence of serum proteins in diabetic patients with and without retinopathy.

Non-enzymatic glycosylation of long-lived proteins results in a characteristic fluorescence, known as protein 'browning'. The degree of fluorescence of skin collagen correlates with retinopathy in diabetes. We have therefore measured the fluorescence of serum albumin and IgG by a sensitive HPLC technique in 69 diabetic patients, 38 with retinopathy and 31 without complications, and in 26 age-matched controls. The fluorescence of the IgG fraction, calculated as the ratio of fluorescence (excitation 360 nm, emission 454 nm) to optical density (280 nm), was elevated in diabetic patients with retinopathy (1.5 +/- 0.5) compared with those without retinopathy (1.1 +/- 0.2, p less than 0.005) and control subjects (1.1 +/- 0.2, p less than 0.005). The fluorescence ratio for the albumin fraction was increased in all diabetic patients (11.2 +/- 2.7) compared with control subjects (8.9 +/- 1.5, p less than 0.001). There was no significant difference in the fluorescence ratios of albumin in those with and without retinopathy. The fluorescence of serum albumin and IgG were not significantly correlated with serum protein glycosylation measured by the fructosamine method.

Biomarkers↗