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R J Schaur

Publications and source records attributed to R J Schaur.

At least 37 records · Page 2Linked to original sources
PubMed1997

Influence of age on the release of reactive oxygen species by phagocytes as measured by a whole blood chemiluminescence assay.

Polymorphonuclear and mononuclear phagocytes play an important role in host defense, but may also cause tissue injury through excessive inflammation. Reactive oxygen species (ROS) are not only directly ore indirectly involved in a wide variety of clinical disorders, such as atherosclerosis, reperfusion injury, pulmonary toxicity and cancer, but they are also important in the aging process. This process is associated with increasing susceptibility to infection. In this study we investigated the influence of age and sex on phagocyte activation by means of a whole blood chemiluminescence (CL) assay. Circulating phagocyte activity was measured in 55 healthy volunteers (24 females, 31 males) aged from 6 to 92 years. Using an automated luminescence system, phagocytes were stimulated by polystyrene beads and Luminol-enhanced CL was determined in terms of peak height and peak time in freshly withdrawn, peripheral venous whole blood. An extremely significant positive correlation (p < 0.0001) between the maximum of light emission after stimulation and increasing age was found. This finding is true for the total population of blood phagocytes as well as for a single cell. In contrast the time of the appearance of the maximum of light emission showed an extremely significant inverse correlation (p < 0.0003) with increasing age. The influence of sex on the CL-parameters showed no significant difference between women and men. It is concluded that the increased susceptibility of circulating phagocytes to oxidative burst in elderly subjects may be the consequence of several biological events. Senescent cells express more and also have new antigens on their surfaces that trigger an autoimmune response. Cellular senescence appears earlier in old organisms. Therefore phagocytes in aging individuals may be increasingly involved in their scavenger tasks that grow with the catabolic bias in cell turnover. Moreover, atherosclerotic alterations in the intima and endothelial lesions are physiologic concomitants of age and may lead to a stimulation of circulating phagocytes.

Adolescent↗
PubMed1997

Effect of oxidative stress by iron on 4-hydroxynonenal formation and proliferative activity in hepatomas of different degrees of differentiation.

It has been shown previously that oxidative stress by ferrous iron in vitro leads to an inhibition of proliferation of murine ascites tumour cells in vivo. This effect is associated with increased lipid peroxidation in terms of formation of the highly reactive aldehyde 4-hydroxynonenal (HNE), which has been shown to inhibit the proliferation of numerous tumours and to induce differentiation. It was the purpose of this article to study the occurrence and metabolism of HNE and its inducibility by oxidative stress in hepatomas of different degrees of differentiation to find further evidence for a possible role of HNE in proliferation and/or differentiation, because it is known that in hepatoma cells with a very low degree of differentiation basal lipid peroxidation is hardly detectable, while in normal hepatocytes the basal level of thiobarbituric acid reactive substances (TBArS) is rather high. MH1C1 hepatoma cells and Yoshida AH-130 hepatoma cells were chosen as highly differentiated and poorly differentiated tumour cells, respectively, and rat hepatocytes served as a control for normal liver phenotype. Ferrous histidinate (Fe/His) did not have a cytotoxic effect on Yoshida and MH1C1 cells, as measured by the LDH release test. In cell culture studies Fe/His revealed a dose dependent inhibition of the proliferation of Yoshida cells. The incorporation of 3H-thymidine into DNA of these cells was also inhibited by Fe/His in a dose-dependent manner, while the precursor uptake into the cytoplasm was unaffected. The basal levels of HNE were in the order: hepatocytes > MH1C1 cells > Yoshida cells. Both hepatocytes and Yoshida cells responded to the presence of Fe/His with increased formation of TBArS. Compared with hepatocytes the response of the Yoshida cells was greatly reduced. The response of cells to Fe/His with respect to HNE formation was decreased in the order: hepatocytes > MH1C1 cells > Yoshida cells, but in this case the differences were not very pronounced. The metabolic capacity of the cells to consume HNE was also decreased in the order: hepatocytes > MH1C1 cells > Yoshida cells. In this case the differences were very pronounced. These findings support the view that Yoshida cells with a low degree of differentiation and a low basal level of HNE are released from an inhibitory effect of HNE operative in hepatocytes and that HNE is causally involved in the iron induced inhibition of proliferation of poorly differentiated hepatoma cells.

Aldehydes↗
PubMed1997

Inhibition of HeLa cell proliferation by 4-hydroxynonenal is associated with enhanced expression of the c-fos oncogene.

Previous studies have shown that the highly reactive aldehyde 4-hydroxynonenal (HNE), a mediator of oxidative stress, can either stimulate or inhibit cell proliferation, depending on the concentration of the aldehyde and the presence of serum. HNE can also induce differentiation of tumour cells in vitro and inhibit the tumour development in vivo. The aim of the study presented was to find out more details about the basic mechanisms by which HNE influences cell growth behaviour. Therefore we analysed the effect of HNE on the transcription of the c-fos gene in HeLa cells, to clarify the pathway by which the aldehyde modulates gene transcription and growth behaviour of the cells. At a supraphysiological concentration (50 microM) the aldehyde caused an enhanced c-fos transcription (as measured by the reverse transcriptase/polymerase chain reaction assay), while it inhibited cell proliferation markedly. Therefore, we assume that among the "early" effects of HNE on cellular growth regulation might be an altered expression of the "early response" genes (c-fos), while a "late" effect might be an altered autocrine/paracrine growth regulation of the cells. This finding on the possible basic mechanisms of the biological effects of HNE together with the already described high toxicity of the aldehyde for cancer cells give support for the further evaluation of the possible use of HNE in cancer biotherapy.

Aldehydes↗
PubMed1996

The influence of trauma on changes in neutrophil granulocyte function assessed by an analysis of granulocyte migration.

We examined the effects of trauma on polymorphonuclear leucocyte (PMN) migratory parameters and PMN elastase release, with the aim of tracing an acute inflammatory reaction from its very beginning to the phase of recovery. Fifteen patients who underwent monotrauma surgery, followed by uneventful healing, served as inflammation model. PMN activation was studied by measuring their readiness to migrate (TMI) and their penetration potency (DC) in a whole blood membrane filter device, in which a chemoattractant depot (FMLP) was integrated. Control chambers lacking FMLP provided parameters of the spontaneous migration. In healthy controls (n = 64), the numbers of invading PMNs decreased continuously from the outermost layer towards the interior of the filter device. FMLP did not influence the mobilization rate of PMNs immigrant from the blood into the filter, but those cells that did migrate penetrated deeper (P < 0.05). After trauma, the spontaneous and FMLP-stimulated DC was increased (P < 0.05). Trauma also tended to inhibit PMN migratory activity episodically; depression of the unspecific immune function (low TMI values) was found on the 3rd (P < 0.0001) and 12th (P < 0.01) postsurgical days. There was no correlation between the migratory parameters and the inflammation parameter, PMN elastase release. Preliminary results indicate that analyses of PMN migratory parameters by a whole blood membrane filter assay could provide a valuable adjunct in monitoring trauma-associated immunologic changes.

Acute-Phase Reaction↗
PubMed1996

Analysis of the in vitro secretory activity of human pituitary adenomas: modification of corticotropin release from adenoma tissue explant cultures by addition of a human plasma ultrafiltrate bioactive fraction.

The lack of control of tumour behaviour is manifested in different ways, depending primarily on the type of tumour. This results in numerous problems of tumour diagnosis and therapy. In the case of "benign" tumours, like pituitary adenomas, in vitro studies are often used for evaluation of the tumour. The use of tissue explant cultures of human pituitary adenomas and the comparison of the feature of cultured tumours with their behaviour in vivo showed that corticotropin is released not only from the tumours associated with Cushing's disease, but also from clinically non-functioning tumours. Hence, it was supposed that the release of corticotropin in vivo from non-secreting tumours is probably under the influence of certain neuroendocrine and/or systemic humoral factors. To test this possibility, samples of 22 tumours were cultured in plain culture medium or in the presence of the "human plasma ultrafiltrate bioactive fraction" (tentatively termed as TBP) prepared by anion-exchange chromatography. In the presence of TBP the release of corticotropin was strongly inhibited in adenomas showing relatively high spontaneous secreting activity in vitro (> 200 ng/l in 24 hours), while immunohistochemistry of these tumours indicated accumulation of corticotropin inside the cells. In contrast, TBP stimulated corticotropin release from tumours that showed relatively low basic corticotropin release (< 200 ng/l in 24 hours), with no obvious change in cellular corticotropin immunoreactivity. Such a dual activity of TBP was not observed for 8 samples of adenomas cultured in the presence of surrounding pituitary tissue, probably because TBP did not affect corticotropin secretion by the normal pituitary cells (as indicated by immunohistochemistry). From these results, it appears that TBP could be one of the humoral factors involved in the regulation of corticotropin release from pituitary adenoma tissue. Its possible involvement in the regulation of corticotropin release from normal pituitary tissue, however, is uncertain.

Adenoma↗
PubMed1995

Assessment of growth inhibition by aldehydic lipid peroxidation products and related aldehydes by Saccharomyces cerevisiae.

The effect of pretreatment with aldehydes on the subsequent colony forming efficiency (CFE) of Saccharomyces cerevisiae was investigated. All 21 aldehydes tested inhibited CFE in a dose-dependent manner. The effective doses, however, differed markedly from 300 mM to 0.07 mM depending on the functional groups and chain length of the aldehydes. Amongst the nine representatives of n-alkanals, formaldehyde was the most potent inhibitor, reducing CFE to 50 per cent at a dose of 0.3 mM (IC50). In the series of 2-trans-alkenals, acrolein was most effective with an IC50 of 0.08 mM and amongst the 4-hydroxy 2-trans-alkenals, 4-hydroxynonenal was most effective with IC50 of 0.07 mM. In general, effectiveness decreased in the order: 4-hydroxyalkenals > 2-alkenals >> n-alkenals. It is proposed that S. cerevisiae is a promising target cell to elucidate further the molecular mechanisms by which aldehydes, particularly the lipid peroxidation product 4-hydroxynonenal, inhibits cell proliferation.

Aldehydes↗
PubMed1995

Released PMN elastase: an indicator of postsurgical uneventful wound healing and early inflammatory complications. A contribution to the search for objective criteria in wound healing monitoring.

Monitoring of postoperative wound healing is important for the early diagnosis of postoperative infective complications in order to decrease morbidity. The purpose of this study was to search for a discriminatory time point between uneventful wound healing and early wound infections after operations for orthopaedic trauma using PMN elastase. This proteolytic enzyme is a biochemical marker for pathological granulocyte stimulation. The two groups of injured patients comprised persons with 'per priman' (pp) wound healing without complications--group 1 (N = 31)--and the early manifestation of a bacterial wound infection 'per secundam' (ps) during the healing phase--group 2 (N = 4). In group 1, surgical trauma was accompanied by an increase in PMN elastase levels reaching the maximum within the first 3 postoperative days; values returned to normal on day 10. In group 2 PMN elastase median levels showed recurring increases throughout. No normal values were observed. There was a highly significant difference (P < 0.01) on days 4 and 5 in group 2 compared with the control group 1. Since PMN elastase can be determined on an autoanalyser, and the enzyme is of proven discriminatory value, it is suggested that this marker should become part of the daily diagnostic routine in the care of the injured.

Adult↗
PubMed1995

Detection of 4-hydroxynonenal (HNE) as a physiological component in human plasma.

4-Hydroxynonenal (HNE) is a major aldehydic product formed by peroxidation of omega 6-unsaturated fatty acids and is regarded as a specific marker of lipid peroxidation. In this paper we demonstrate that there is a physiological steady-state concentration of HNE in human venous blood plasma. For the quantitative determination of HNE a modified version of an existing, but tedious and time-consuming HPLC method was developed. The extraction of aldehydic hydrazones from plasma was performed using an Extrelut column and the separation step by thin-layer chromatography was replaced by column chromatography on silica gel. The concentration of HNE in human blood plasma was in the same range as the concentration that was found to inhibit the proliferation of cells of the peripheral tissues, i.e., endothelial cells and fibroblasts in vitro. In an experiment with reduced peripheral blood flow a temporary significant increase of HNE was observed during reperfusion. It was concluded that lipid peroxidation occurs in peripheral tissues of humans following temporary congestion of venous blood flow.

Adult↗
PubMed1994

Polymorphonuclear leucocyte migration response in uneventful wound healing following trauma surgery. A contribution to the search for objectifiable criteria in wound healing monitoring.

In a study of the clinical importance of polymorphonuclear granulocytes (PMN) for the monitoring of wound healing we investigated the postsurgical course of nine patients all of whom had undergone trauma surgery and had no wound complications. The "stimulated random PMN locomotion" was evaluated by a new migration filter device which preserves the cells in their genuine priming state, simulating in vivo conditions. The percentage of all activated PMN, expressed by the total migration index (TMI) reflected the highest median immediately after surgery (Zmax = 30.1%) and dropped to the lowest value on day 13 (Zmin = 13.9%). The mean invasion depth (T/2) of the cells along the migration distance into the filter showed only slight variations over time. The neutrophil migration activity (NMA), described by T/2 and TMI, behaved in a similar way to TMI. In studying physiological healing, preliminary results indicate that TMI, which expresses PMN activation, is an efficient tool in the postoperative monitoring of patients, and might in the future serve as a basis for an early warning system for wound healing complications.

Adult↗
PubMed1994

Mutual dependence of growth modifying effects of 4-hydroxynonenal and fetal calf serum in vitro.

Recently, the hypothesis has been put forward that 4-hydroxynonenal (HNE), an aldehydic product of lipid peroxidation, contributes to the mechanisms of oxygen toxicity and to the selective pressure exerted by exposure to hyperoxia. Here it has been studied whether HNE itself is involved in mechanisms that convey increased resistance of the cells to the toxicity of HNE. The following four cell lines, different in their basic biological features, were used: nonmalignant Chinese hamster lung fibroblasts V79 (established cell line), human carcinoma HeLa (established cell line), pigmented murine melanoma B16f10 (primary culture), and amelanotic murine melanoma B16BL6 (primary culture). The cells were pretreated in vitro with a toxic dose of HNE (50 microM), and afterwards the effect of a second exposure to the same dose of HNE on 3H-thymidine incorporation was examined. Cells were cultured in the absence and in the presence of fetal calf serum (FCS), because it had been shown that a growth modifying effect of HNE depends on an unknown serum factor. The results showed that, regardless of the type of cells, preculturing them with 50 microM HNE in the presence of serum changed the reactivity of the cells to added serum as well as to additional HNE treatment. Thus, HNE precultured cells incorporated less 3H-thymidine in the presence of serum than if cultured under serum-free conditions. On the other hand, HNE precultured cells became less sensitive to further HNE treatment, but only if cultured in the presence of serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehydes↗
PubMed1994

The lipid peroxidation product 4-hydroxynonenal is formed by--and is able to attract--rat neutrophils in vivo.

4-Hydroxynonenal (HNE), a major aldehydic product of lipid peroxidation, is a chemoattractant for neutrophilic polymorphonuclear granulocytes in vitro. The question was studied, whether HNE is formed during the ingress of neutrophils in the Sephadex model of inflammation. The polydextrane Sephadex G-200, which causes an acute aseptic traumatic inflammation, was injected subcutaneously into rats. The implants were excised 6-36 hours later, and the neutrophils separated from the exsudate by centrifugation. After extraction with dichloromethane HNE was identified in the exsudate by non-derivative reversed phase HPLC in combination with on-line uv-spectroscopy. The concentration of HNE in the inflammatory focus did not correlate with the number of neutrophils present. While the peak of HNE coincided with the time point of the highest turnover rate of neutrophils (0.13 microM at 6 hrs after implantation), the highest number of neutrophils (about 100 million cells) occurred not earlier than 18 hrs later (24 hrs after onset of inflammation). When neutrophils were isolated from the inflammatory focus and stimulated with Zymosan, they were able to produce HNE in vitro depending on the time of isolation. The highest production of HNE (0.17 microM) by phagocyting neutrophils was observed at the shortest inflammation time studied (3 hrs). In order to compare these results with the oxidative burst of neutrophils the formation of superoxide was also measured by the cytochrome c reduction assay in vitro. The maximum of the production rate of superoxide anion was observed at the same inflammation time (6 hrs), when the HNE maximum occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehydes↗
PubMed1993

Stimulation of HeLa cell growth by physiological concentrations of 4-hydroxynonenal.

The aim of this study was to analyze the growth response of HeLa cells over a prolonged period of time to a single exposure of physiological and supraphysiological concentrations of 4-hydroxynonenal (HNE), a peroxidation product of omega-6-polyunsaturated fatty acids. Furthermore, the growth modulating effect of serum factors, particularly albumin, on the growth pattern was examined. The effects of HNE on the growth rate and viability of the cells, as well as on the incorporation of labelled amino acids were monitored daily over a period of four days. Fetal calf serum not only had a growth stimulating effect but also modulated the action of HNE. In neither respect was albumin able to substitute for serum indicating that the influence of serum was not exerted via an albumin-HNE conjugate. HNE had a clear dose-dependent effect and a distinction could be made between a supraphysiological concentration (100 microM), which was primarily cytotoxic and a physiological range (below 10 microM) which showed growth modulatory effects. These effects consisted of a transient inhibition in the initial phase of the cell growth, which under optimal conditions (in presence of serum) was followed by a period of increased proliferation, compared to untreated control cultures, until confluence was attained. It is suggested that HNE is not only a toxic product of lipid peroxidation, but a physiological growth regulating factor as well.

Aldehydes↗
PubMed1993

[Biochemical wound monitoring. PMN elastase in different healing stages after trauma surgery-orthopedic interventions].

Laboratory parameters are of proven value in the diagnosis of early postsurgical infections, since clinical aspects cannot always be clearly defined. Neutrophil granulocytes (PMN) are major inflammatory cells taking effect following ingestion and degradation of foreign material, such as bacteria and cell debris, for example after mechanical trauma. In patients who had undergone surgery we monitored the course of plasma PMN elastase in uncomplicated wound healing (n = 22), in uncomplicated wound healing associated with secondary infections (n = 6), and in defective wound healing (manifestation of a bacterial wound infection: n = 3; wound infection already manifest at the time of entry on study: n = 11). Surgical trauma was accompanied by an increase in PMN elastase and C-reactive protein (CRP) in all patients studied, reaching a maximum within the first 3 postsurgical days. When a bacterial wound infection became manifest during the course of healing there was a highly significant difference on the 4th postsurgical day (p < 0.01) compared with the group with uncomplicated healing. Since PMN elastase can now be determined automatically with an autoanalyser and a commercial kit and its discriminatory time point is as soon as 4-5 days after surgery, it is suggested that this marker should be determined routinely together with CRP in traumatology.

Adult↗
PubMed1992

Possible involvement of myeloperoxidase in lipid peroxidation.

1. Exposure of liposomes to the MPO-H2O2-Cl- system results in oxidation of lipids. Malondialdehyde and 4-hydroxynonenal are formed. 2. Oxidation of liposomes by stimulated rat neutrophils, assessed by malondialdehyde formation, is inhibited by KCN. This indicates involvement of MPO in the process. 3. The MPO-H2O2 system oxidizes mildly LDL but in the presence of chloride a propagation phase, with a rapid increase of conjugated diene formation, was observed.

Animals↗
PubMed1991

Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes.

Lipid peroxidation often occurs in response to oxidative stress, and a great diversity of aldehydes are formed when lipid hydroperoxides break down in biological systems. Some of these aldehydes are highly reactive and may be considered as second toxic messengers which disseminate and augment initial free radical events. The aldehydes most intensively studied so far are 4-hydroxynonenal, 4-hydroxyhexenal, and malonaldehyde. The purpose of this review is to provide a comprehensive summary on the chemical properties of these aldehydes, the mechanisms of their formation and their occurrence in biological systems and methods for their determination. We will also review the reactions of 4-hydroxyalkenals and malonaldehyde with biomolecules (amino acids, proteins, nucleic acid bases), their metabolism in isolated cells and excretion in whole animals, as well as the many types of biological activities described so far, including cytotoxicity, genotoxicity, chemotactic activity, and effects on cell proliferation and gene expression. Structurally related compounds, such as acrolein, crotonaldehyde, and other 2-alkenals are also briefly discussed, since they have some properties in common with 4-hydroxyalkenals.

Aldehydes↗
PubMed1990

Ultraviolet fluorescence of human sera: I. Sources of characteristic differences in the ultraviolet fluorescence spectra of sera from normal and cancer-bearing humans.

The ultraviolet fluorescence emission spectra of sera from apparently healthy persons and of sera from cancer patients frequently show significantly different curve shapes. A biparametric fluorescence method has been developed to use these deviations to detect patients with malignant diseases (Clin Chem 1986;32:1974-8). However, the pathobiochemical reasons for these differences of diagnostic importance have thus far been unclear. To find a relevant explanation for the described effect, we focused our interest on human serum proteins, the materials mainly responsible for the intrinsic fluorescence of sera in this spectral region. Human sera of various protein compositions were selected according to their protein pattern, determined by cellulose acetate electrophoresis, and their intrinsic fluorescence properties were investigated. We found that the emission spectra of human sera were correlated with their relative protein compositions, albumin and alpha-2 globulins being the most significantly correlated with the fluorescence intensity ratios. Because increased percentages of alpha-2 globulins and decreased percentages of albumin frequently accompany malignancies, we suggest that this condition accounts for the differences between the emission spectra of sera from normal and cancer-bearing humans.

Alpha-Globulins↗
PubMed1989

Iron-induced lipid peroxidation and inhibition of proliferation in Ehrlich ascites tumor cells.

The purpose of this study was to find further experimental evidence for the postulated negative association between the extent of lipid peroxidation in tumor cells and their proliferative behavior. After incubation of Ehrlich ascites tumor cells at 37 degrees C for 30 min with increasing concentrations of Fe(II) histidinate (Fe/His) the following parameters were determined: the formation of lipid hydroperoxides was measured fluorimetrically after reaction with dichlorofluorescein; 4-hydroxynonenal was determined by reversed-phase high-pressure chromatography after derivatization with dinitrophenylhydrazine; as a third parameter of lipid peroxidation the formation of 2-thiobarbituric-acid-reactive substances was determined. The proliferative activity was determined by measuring the growth rate in vivo after reimplantation i.p. of the tumor cells into mice. Trypan-blue exclusion tests for viability were performed before reimplantation. The reliability of the trypan-blue exclusion tests was checked by comparing the results with another parameter of viability, the release of the cytosolic enzyme lactate dehydrogenase. The concentration both of lipid hydroperoxides and of 2-thiobarbituric-acid-reactive substances showed a biphasic dependence on the concentration of Fe/His with maximal increase at iron concentrations of 0.25 mM and 0.1 mM respectively. 4-Hydroxynonenal, in contrast, showed a continuous increase up to 41.1 nM (corresponding to 0.58 pmol/10(9) cells) with increasing iron concentration in the range from 0.1 mM to 0.6 mM. The total number of tumor cells, when determined 5 days after reimplantation, continuously decreased with increasing iron concentration, showing half-maximal inhibition at about 0.22 mM Fe. The exclusion of the trypan-blue dye was unaffected by the presence of iron at any concentration used. Similarly, iron had no influence on the release of lactate dehydrogenase. The results support the hypothesis that 4-hydroxynonenal may act as an inhibiting messenger between endogenic lipid peroxidation and proliferation.

Animals↗