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Biomedical subjects

G Reibnegger

Publications and source records attributed to G Reibnegger.

At least 55 records · Page 3Linked to original sources
PubMed1995

Serum-soluble receptors for tumor necrosis factor-alpha and interleukin-2, and neopterin in acute rheumatic fever.

Immune activation may play an important role in the pathogenesis of acute rheumatic fever (ARF). The objective of the present study was to investigate serum concentrations of various markers of immune activation in ARF patients. Sera of 32 patients with ARF were investigated, 20 of them in follow-up. Radioimmunoassay was used to quantify neopterin and ELISA for the measurement of 55-kDa-type soluble tumor necrosis factor receptor (sTNF-R) and soluble interleukin-2 receptor (sIL2-R). Markers of immune activation were found to be raised in 48% (sTNF-R), 28% (sIL2-R), and 78% (neopterin) of patients at the onset of ARF. There were significant correlations between the concentrations of neopterin and sTNF-R (rs = 0.60, P < 0.001) or sIL2-R (rs = 0.35, P < 0.05). Higher neopterin concentrations were found in patients with combined aortic and mitral insufficiency than in patients with mitral valve lesions alone (U = 2.67, P < 0.05) or without valve lesion (U = 2.36, P < 0.05). Increased concentrations of neopterin, sTNF-R, and sIL2-R demonstrate activation of the cellular immune system in patients with ARF. Higher serum neopterin concentrations are associated with development of combined aortic and mitral insufficiency during the first episode of ARF.

Acute Disease↗
PubMed1995

Survival differences in Austrian patients with the acquired immunodeficiency syndrome.

We investigated the association of clinical and demographic factors on survival of the 901 AIDS cases diagnosed until 31 December 1992 and reported to the Austrian Health Authorities up to 20 January 1994. The overall estimated median survival of patients with AIDS increased substantially from 8 months in 1987 to 16 months in 1988, although this increase was not significant by the log-rank test. However, the differences in hazard rates were larger at the beginning of the survival curve: between 1987 and 1988 the proportion surviving at 1 year increased from 41 to 62%, compared to an increase of the proportion surviving at 2 years from 30 to 35% (Breslow test, p value 0.008). AIDS patients diagnosed between 1988 and 1992 (n = 755) were analyzed in more detail. Multivariate survival analysis revealed a shorter survival for those with residence in Eastern Austria, recipients of blood products, individuals with unknown transmission risk, those presenting with two AIDS indicator diseases and those with higher age at AIDS diagnosis. Candidal esophagitis as AIDS indicator disease was associated with longer survival. One hundred eighty-eight of the 755 AIDS patients (24.9%) died within the first 3 months after diagnosis of AIDS. We conclude that the survival time for AIDS patients has improved considerably after 1987, but survival is still very poor. Several factors have been shown to predict survival of patients with AIDS in Austria. Death within the first 3 months after the diagnosis of AIDS occurred at a relatively high frequency in Austrian AIDS patients. This may be caused by difficulties in the use of health care facilities or by the lack of awareness of HIV infection before diagnosis of AIDS either by patient or care provider.

AIDS-Related Opportunistic Infections↗
PubMed1995

Effects of pteridines on luminol-dependent chemiluminescence induced by chloramine-T.

Pteridines are ubiquitous in living organisms, but little is known about their biological functions. Different pteridines were tested for their ability to modulate luminol-dependent chemiluminescence induced by chloramine-T at pH = 7.5 and at a concentration of 100 microM for each pteridine. We observed striking differences between the compounds; whereas reduced pteridine species were generally potent scavengers, aromatic pteridines were weak to strong enhancers of the chemiluminescence. Taking into account the detailed chemical structure of the molecules, by multiple linear regression analysis a simple index was constructed that allows prediction of the effects of the different pteridines with high accuracy (linear correlation coefficient between predicted and observed values r = 0.89). The effects of different pteridines on free radical-induced chemiluminescence might bear biological significance since, for example, certain pteridines take part in enzymic reactions involving free-radical intermediates, or are related to the activation of macrophages in close relationship with the oxidative burst.

Animals↗
PubMed1995

Serum nitrite plus nitrate in infection with human immunodeficiency virus type-1.

To get a measure of the extent of induction of nitric oxide synthase in infection with human immunodeficiency virus type-1 (HIV-1) in vivo, we estimated serum nitrite plus nitrate concentrations in 110 HIV-1 infected individuals compared to 76 blood donors. To monitor cytokine action and to measure induction of pteridine synthesis, we determined in parallel neopterin, biopterin, soluble tumor necrosis factor-alpha receptor 55 and 75, and beta 2-microglobulin. Serum nitrite plus nitrate concentrations were elevated in patients as compared to blood donor controls. In sera of patients, nitrite plus nitrate levels correlated significantly with neopterin, soluble tumor necrosis factor receptor 55 and 75, and beta 2-microglobulin. Nitrite plus nitrate levels were higher and correlations were stronger in groups of patients with lower CD4+ cell count. These results suggest that cytokine-mediated nitric oxide synthesis occurs in individuals with HIV-1 infection.

Adult↗
PubMed1995

Detection of bacterial pyrogens on the basis of their effects on gamma interferon-mediated formation of neopterin or nitrite in cultured monocyte cell lines.

In a number of mammalian cell types, pteridine biosynthesis from guanosine 5'-triphosphate and formation of nitric oxide from L-arginine are induced by gamma interferon (IFN-gamma) and bacterial lipopolysaccharide (LPS). We assessed the possibility of using such metabolic alterations for the in vitro detection of pyrogens. Products from gram-negative and gram-positive bacteria and related synthetic compounds were tested for their potential to induce either of these pathways. Stimulation of pteridine biosynthesis was monitored as the formation of neopterin in the human myelomonocytic cell line THP-1. The formation of nitric oxide was determined as nitrite in murine J774A.1 macrophage cultures. The substances tested included toxic and detoxified parts of LPS and lipid A from Escherichia coli, Salmonella typhimurium, Salmonella minnesota, and Klebsiella pneumoniae as well as lipoteichoic acid and toxic shock syndrome toxin 1 from Staphylococcus aureus. Furthermore, two cell wall compounds from Mycobacterium tuberculosis, trehalose 6,6'-dimycolate and N-acetylmuramyl-L-alanyl-D-isoglutamine, which are active components of Freund's adjuvant, were used. When applied as a single stimulus, only the whole LPS molecule potently stimulated neopterin or nitrite formation. Lipid A and products from gram-positive bacteria were weakly active. For neopterin formation, lipid A required the presence of fetal calf serum. Besides detoxified LPS and independently from the presence of serum, all bacterial compounds tested strongly increased the effects mediated by IFN-gamma. Our results show that bacterial pyrogens can be detected by monitoring the formation of neopterin or nitrite. This may provide a basis for the development of an in vitro assay for the detection of pyrogenic contamination with the aim of replacing the currently used animal test.

Animals↗
PubMed1995

Serum soluble markers of immune activation and disease activity in systemic lupus erythematosus.

We investigated a possible association between markers of immune activation and disease activity in 52 patients with systemic lupus erythematosus (SLE). Serum concentrations of neopterin, beta-2-microglobulin, 55 kD-type soluble tumor necrosis factor receptor, soluble interleukin-2 receptor and soluble CD8 were compared to the Index of European Consensus Lupus Activity Measurement (ECLAM). All markers of immune activation, except sCD8, significantly correlated with ECLAM. Stepwise multiple linear regression analysis revealed erythrocyte sedimentation rate and neopterin to correlate best with ECLAM (multiple correlation coefficient = 0.74, P < 0.001). The study shows that serum neopterin concentrations are a useful independent index for disease activity in SLE. The finding of enhanced concentrations of various parameters of immune activation in patients confirm a role of the T cell and macrophage activation in the pathogenesis of SLE.

Adolescent↗
PubMed1995

Predictive value of urinary neopterin in patients with lung cancer.

Concentrations of neopterin, which is produced by human monocytes/macrophages when stimulated by gamma-interferon, were measured in urine specimens from 72 patients with lung cancer at diagnosis. Other routine clinical and laboratory variables were concomitantly determined. Neither neopterin nor any other laboratory variable studied showed a significant correlation with clinical indicators of the disease (morphologic type, tumour stage, grading, lymph node status, presence of distant metastases). The cancer patients were followed up for up to 10 years, and the abilities of all variable to predict fatal outcome were assessed. In univariate survival analyses, all clinical indicators except morphologic type (P = 0.86) were significant predictors of survival (P < 0.002), but of all the laboratory variables studies, only neopterin was significantly predictive (P = 0.0013). By multivariate survival analysis, a combination of four variables was found to jointly predict survival: lymph node status (P = 0.003), multivariate model), tumour stage (P = 0.0006), grading (P = 0.0047) and neopterin (P = 0.0047). The data suggest that certain aspects of immune activation may have adverse consequences for the prognosis of patients with lung cancer.

Adult↗
PubMed1995

7,8 Dihydroneopterin inhibits low density lipoprotein oxidation in vitro. Evidence that this macrophage secreted pteridine is an anti-oxidant.

Neopterin and its reduced form, 7,8 dihydroneopterin are pteridines released from macrophages and monocytes when stimulated with interferon gamma in vivo. The function of this response is unknown though there is an enormous amount of information available on the use of these compounds as clinical markers of monocyte/macrophage activation. We have found that in vitro 7,8-dihydroneopterin dramatically increases, in a dose dependent manner, the lag time of low density lipoprotein oxidation mediated by Cu++ ions or the peroxyl radical generator 2,2'-azobis (2-amidino propane) dihydrochloride (AAPH). 7,8-Dihydroneopterin also inhibits AAPH mediated oxidation of linoleate. The kinetic of the inhibition suggests that 7,8-dihydroneopterin is a potent chain breaking antioxidant which functions by scavenging lipid peroxyl radicals. No anti-oxidant activity was observed in any of the oxidation systems studied with the related compounds neopterin and pterin.

Adult↗
PubMed1994

Increased production of immune activation marker neopterin by colony-stimulating factors in gynecological cancer patients.

Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been introduced in the treatment of chemotherapy-induced neutropenia. Effects of these CSFs on the cellular immune system were evaluated in 38 neutropenic gynecological cancer patients during chemotherapy. In addition to restoring the leukocyte count, GM-CSF--to a greater extent than G-CSF--also induced neopterin, a sensitive marker of macrophages activated by interferons. This effect was confirmed in vitro by investigating the effects of these CSFs on interferon-gamma-mediated pathways in THP-I human myelomonocytic cells. The results suggest activation of immune effector cells by GM-CSF.

Adult↗
PubMed1994

Enhancement of hydrogen peroxide-induced luminol-dependent chemiluminescence by neopterin depends on the presence of iron chelator complexes.

We have previously shown that neopterin, 6-D-erythro-trihydroxypropyl-pteridine, synthesized by human monocytes/macrophages upon stimulation by interferon-gamma, enhances toxicity of reactive oxygen at neutral or slightly alkaline pH (7.5), but not at acidic pH (below 6.5). In the present study, we explored in more detail the necessary requirements for neopterin to modulate the effects of hydrogen peroxide in a luminol-dependent chemiluminescence assay. We demonstrate that neopterin enhances hydrogen peroxide effects only in the presence of iron chelator complexes like iron-(III)- or iron-(II)-EDTA or iron-(III)-DTPA. Thus, iron chelator complexes together with neopterin may play an important role in macrophage-mediated effector mechanisms.

Biopterins↗
PubMed1994

Increased concentrations of soluble tumor necrosis factor receptor 75 but not of soluble intercellular adhesion molecule-1 are associated with the decline of CD4+ lymphocytes in HIV infection.

Immune activation seems to be involved in the pathogenesis of human immunodeficiency virus (HIV) infection. The immune activation markers neopterin and beta 2-microglobulin can predict the future rate of the decrease in CD4+ T cells. In a longitudinal study, we assessed whether the decline in the CD4+ T-cell count is associated with increased concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble tumor necrosis factor receptor 75 (sTNFR 75), compared to increased concentrations of beta 2-microglobulin and urinary neopterin. Forty-seven individuals representing all stages of HIV infection were followed-up for a mean of 12.7 months (range, 8 to 16 months). The percentage of the change of the CD4+ T-cell count from study entry to study end ranged from -97 to +98%; the median was -33%. Concentrations of urinary neopterin, sTNFR 75, and beta 2-microglobulin correlated with the percentage of the change of the CD4+ T-cell count from study entry to study end (r = -0.45, confidence interval (CI) -0.65 to -0.19; r = -0.42, 95% CI -0.63 to -0.15; and r = -0.416, 95% CI -0.62 to -0.15), but those of sICAM-1 did not. This difference was found despite significant correlations between sICAM-1 and sTNFR 75 and beta 2-microglobulin. Levels of sICAM-1 obtained at study entry correlated with levels of sICAM-1 obtained at study end (r = 0.46, 95% CI 0.17 to 0.68). In a multivariate linear regression analysis, urinary neopterin and sTNFR 75 were jointly significant for the percentage of the change of the CD4+ T-cell count. These results suggest that sTNFR 75 is a useful marker to estimate disease progression in HIV infection, whereas sICAM-1 does not seem to provide any information related to the decline of the CD4+ T-cell count.

Adult↗
PubMed1994

Increased concentrations of neopterin in carotid atherosclerosis.

Activation of T-cells and macrophages may play a role in the pathogenesis of atherosclerosis. Therefore, serum concentrations of the immune activation markers neopterin and soluble interleukin-2 receptor were compared with routine laboratory parameters, candidate risk variables and degree of carotid atherosclerosis. Study subjects were 561 individuals (293 men and 268 women) aged between 50 and 79 years who were enrolled in a cross-sectional community based study (Ischemic Heart Disease and Stroke Prevention Study, Bruneck, Italy). Extent of carotid atherosclerosis was quantitated by an ultrasound B-mode procedure based scoring system. Detailed physical examination and quantification of laboratory and candidate risk variables were performed. By univariate as well as multivariate statistical analyses, serum concentrations of neopterin but not soluble interleukin-2 receptor were significantly higher in subjects with carotid atherosclerosis (men, 8.5 +/- 2.7 nmol/l neopterin; women, 9.6 +/- 3.3) than in those without (men, 6.7 +/- 2.3, P < 0.0001; women, 7.5 +/- 2.3, P < 0.0001). The data show that the macrophage-derived immune activation marker neopterin is closely correlated with the extent of carotid atherosclerosis. Chronic activation of immune cells, preferentially of macrophages, may play a key role in atherogenesis and/or progression of atherosclerosis.

Aged↗
PubMed1994

Correlation of body mass index with urinary neopterin in individuals infected with human immunodeficiency virus.

We assessed correlations between body mass index and plasma lipids, immune activation markers and the CD4+ T-cell count. The subjects of this cross-sectional study were randomly selected and comprised all those who attended the AIDS Out-Patient Clinic at the University Hospital in Innsbruck in March and April 1992. Patients with signs and symptoms of acute bacterial and secondary opportunistic infections were excluded. We investigated 63 individuals with HIV infection of whom 35 were asymptomatic, 8 had oral candidiasis, 4 had constitutional signs and symptoms and 16 had AIDS, for an association among body mass index, urinary neopterin, soluble tumor necrosis factor receptors (sTNFRs), plasma lipids, and the numbers of CD4+ T cells. The body mass index correlated inversely with urinary neopterin (rs = -0.42, p = 0.0009) and weakly with the numbers of CD4+ T cells (rs = 0.29, p = 0.02) but not with plasma lipids, sTNFRs and beta 2-microglobulin. The results show that body mass index correlates with immune activation. The data suggest that endogenous formation of interferon-gamma may be an important mediator of wasting in HIV infection, since this cytokine is responsible for the observed elevation of neopterin concentrations in body fluids.

Adult↗
PubMed1994

HIV myelopathy.

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Biopterins↗
PubMed1994

Decreased plasma concentrations of HDL cholesterol in HIV-infected individuals are associated with immune activation.

We investigated 63 individuals with HIV infection, 34 of whom were asymptomatic (nine had oral candidiasis, four had constitutional signs and symptoms, and 16 had AIDS), for plasma lipids, soluble tumor necrosis factor receptor 75 (sTNF-R75) and other immune activation markers, namely urinary neopterin, beta 2-microglobulin, and the CD4+ T cell count. The median CD4+ T cell count was 318 x 10(6)/L. All individuals were allowed to have light breakfast in the morning; the venipuncture for the plasma lipids was done between 11 a.m. and 3 p.m.. Decreased plasma concentrations were found for total cholesterol, and HDL and LDL cholesterol in 3.2%, 46%, and 56% of the subjects, respectively. Plasma triglyceride levels were increased in 31.7% of the study population. The frequency and the extent of the decrease of HDL and LDL cholesterol and the increase in triglyceride levels were greater in those with a CD4+ T cell count below the median (p = 0.003, p = 0.05, and p = 0.01); when comparing individuals with CD4+ T cell counts above and below 500 x 10(6)/L (19 individuals), a difference was only found for HDL cholesterol (p = 0.01). Plasma levels of triglycerides correlated significantly however weakly with serum concentrations of sTNF-R75 (rs = 0.32, p = 0.01) but not at all with urinary neopterin or serum beta 2-microglobulin. HDL cholesterol correlated inversely with sTNF-R75 (rs = -0.53, p < 0.0001) and to a lesser extent with urinary neopterin (rs = -0.46, p = 0.0003) and beta 2-microglobulin (rs = -0.34, p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗