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Biomedical subjects

G Reibnegger

Publications and source records attributed to G Reibnegger.

At least 109 records · Page 6Linked to original sources
PubMed1991

Postmortem neopterin concentrations: comparison of diagnoses with and without cellular immunological background.

Increased neopterin levels in urine and serum of living humans indicate an activation of the cellular immune system. We investigated 119 urine and 48 serum samples from 129 corpses taken at necropsy; 29 cases with a background of cellular immune activation were compared to 100 corpses with no such indication. Our investigations show the feasibility of postmortem neopterin measurements. However, different kinetics of serum and urine concentrations after death were observed. In addition, the data show that urine and serum neopterin concentrations were significantly higher when cellular immunological abnormalities were present when compared to the control group and to living healthy controls. The findings suggest, that increased postmortem urine neopterin concentrations in necropsy indicate pathological processes linked with cellular immune activation.

Adolescent↗
PubMed1991

Neopterin and beta 2-microglobulin as prognostic indices in human immunodeficiency virus type 1 infection.

The great majority of individuals with human immunodeficiency virus type 1 (HIV-1) infection presents with no signs or symptoms, or only lymphadenopathy. To initiate prophylactic measures in time it is necessary to establish risk criteria. CD4+ cell counts are significant predictors. Supplementary methods to improve the predictive information of CD4+ cell counts are still required. In addition, CD4+ cell counting is laborious, expensive, and restricted to specialized laboratories. Thus, there is also a place for more easily performed laboratory tests with similar predictive value as CD4+ cell counts. Neopterin and beta 2-microglobulin levels proved to be significant predictors of AIDS risk in HIV-1 seropositives. The predictive value of both parameters is equal to CD4+ cell counts and both markers are significant joint predictors in addition to CD4+ cell counts. Measurement of the parameters is done in serum (neopterin and beta 2-microglobulin) or urine (neopterin) specimens which reduces the risk of HIV-1 transmission compared to handling of whole-blood samples as it is required for cell counting. Although more studies are needed, especially in developing countries and in persons receiving zidovudine, it can be recommended to use neopterin and beta 2-microglobulin as additional marker to estimate AIDS risk in HIV-1 seropositive individuals. Moreover, both markers may be useful for this purpose without CD4+ cell counts if cell counting is not available.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Increased endogenous interferon-gamma and neopterin correlate with increased degradation of tryptophan in human immunodeficiency virus type 1 infection.

Reduced tryptophan and increased kynurenine concentrations have been reported in patients with human immunodeficiency virus type 1 (HIV-1) infection. From in vitro data it appears that activated indoleamine 2,3-dioxygenase (IDO) is involved in this metabolic change. IDO is inducible by interferon-(IFN)-gamma. We compared serum concentrations of IFN-gamma and neopterin (the biosynthesis of which is also inducible by IFN-gamma) with serum, tryptophan and kynurenine of 42 patients with HIV-1 infection. IFN-gamma, neopterin and kynurenine levels were significantly increased compared to HIV-1 seronegative controls whereas tryptophan was significantly decreased. Various significant correlations were found between tryptophan, kynurenine, IFN-gamma and neopterin concentrations. Highest degree of correlation was found between neopterin, IFN-gamma and the kynurenine per tryptophan quotient which is the ratio between the product and the substrate concentration of IDO. The data indicate that decreased tryptophan in HIV-1 seropositives may result from chronic immune activation and can be referred to increased activation of IDO.

Adult↗
PubMed1991

Negative correlation between blood cell counts and serum neopterin concentration in patients with HIV-1 infection.

Hematopoietic disturbances are common in patients with HIV-1 infection. Recent studies on immune activation markers such as neopterin demonstrate that HIV-1 infection is associated with chronic immune activation. We investigated a possible association between serum neopterin concentrations and blood cell counts (CD4+ T cells, white blood cells, platelets, red blood cells) and hemoglobin and hematocrit in 94 HIV-1-seropositive individuals [52 Walter Reed (WR) stage 1, 31 WR2, one WR5, and 10 WR6]. There were significant negative correlations between neopterin concentrations and CD4+ T cells, hemoglobin, hematocrit and platelets. These correlations were also significant if either only WR1 and WR2 patients or the entire set of data were considered for calculations. Thus, hematological abnormalities are associated with chronic immune activation in patients with HIV-1 infection. Large amounts of neopterin are released by human macrophages on stimulation with interferon-gamma (IFN gamma), and tumor necrosis factor alpha (TNF alpha) further enhances the effect of IFN gamma. Therefore, our data suggest that activated immune cells and specific cytokines such as IFN gamma and TNF alpha are involved inhibiting hematopoiesis.

Biopterins↗
PubMed1991

Markers for disease progression in intravenous drug users infected with HIV-1.

We evaluated the number and percentage of CD4+ T cells, the ratio of CD4+ T cells to CD8+ T cells, the serum levels of beta 2- microglobulin and urinary levels of neopterin for their ability to predict disease progression (defined as clinical AIDS and/or oral candidiasis in combination with a CD4+ T cell count less than 400 x 10(6)/l). Thirty-eight intravenous drug users (IVDU) infected with HIV-1 without HIV-1-related symptoms were followed for a median observation period of 45 months. Cumulative incidence of disease progression was computed by the product-limit approach. The CD4+: CD8+ T-cell ratio (P = 0.001), the number (P = 0.002) and percentage (P = 0.05) of CD4+ T cells, and urinary neopterin (P = 0.007) were significant predictors for disease progression. Serum beta 2-microglobulin, which has been found to be of similar prognostic value as neopterin in homosexual men, did not show predictive power in this study of IVDU. The urinary neopterin concentrations obtained at entry of the study correlated with the values of the CD4+:CD8+ T-cell ratio and number and percentage of CD4+ T cells which were obtained at the end of the follow-up. These findings should help to identify, among HIV-1-infected IVDU, those at high risk of disease progression.

Adult↗
PubMed1991

Posttransplant neopterin excretion in renal allograft recipients--a reliable diagnostic aid for acute rejection and a predictive marker of long-term graft survival.

During the immediate posttransplant period, daily measurements of urinary neopterin, which is produced by stimulated macrophages, were evaluated in 294 consecutive recipients of renal allografts for their diagnostic value in acute graft rejection. The ability of mean and peak neopterin excretion values to predict long-term graft survival was analyzed on the basis of an eight-year follow-up. Immunosuppressive therapy (cyclosporine +/- prednisone versus azathioprine + prednisone) and initial nonfunction did not influence neopterin excretion. In patients with rejection episodes and in those with infections, neopterin levels were significantly increased. Diagnostic sensitivity and specificity with regard to rejection diagnosis were assessed for different levels of neopterin. By statistical analysis, a significant association between increased neopterin and higher risk of rejection was found, which was particularly pronounced in patients receiving cyclosporine. Increase in neopterin excretion preceded clinical rejection diagnosis by up to four days. Peak neopterin values above 800 mumols/mol urinary creatinine observed during the posttransplant period, were associated with significantly poorer graft survival. A multivariate analysis showed that peak neopterin levels, age of patients, and early posttransplant presence/absence of acute rejection were significant and independent joint predictors for long-term graft survival. Measurement of neopterin can be of help as an additional marker in early diagnosis of renal allograft rejection, and high neopterin values during the initial posttransplant period are associated with poorer long-term graft survival.

Adolescent↗
PubMed1991

Change in HIV-antibody seroprevalence rates in i.v. drug dependent prisoners.

In 1985 a high HIV-seroprevalence (44.2%) was found in a cohort of parenteral drug addicted prisoners in Innsbruck, Austria. In a longitudinal study from March 1985 to March 1989 we investigated the epidemiology of HIV-infection as well as possible changes in the drug taking behaviour of this defined population at risk. During the study HIV-seroprevalence rates in drug dependent prisoners showed a statistical decrease to 30%. A concomitant increase in admission to any kind of therapy programmes as well as an increasing change from 'heavy use' (mainly taking heroin i.v.) to 'non-heavy use' (mainly taking drugs orally) could be noted. The influence of preventive measures, such as comprehensive AIDS-information, special therapy programmes including the methadone substitution programme, and the unrestricted availability of needles and syringes is discussed.

Adolescent↗
PubMed1991

Immune activation and the anaemia associated with chronic inflammatory disorders.

Chronic inflammatory disorders are associated with an increased risk of patients developing anaemia. There is some evidence that cytokines released during cell-mediated immune responses are capable of inhibiting bone marrow haematopoiesis. In vitro, interferon gamma and tumour-necrosis factor alpha inhibit growth of erythroid precursor cells. The mode of action of these cytokines is probably associated with their antiproliferative capacity. Decrease of serum iron and increase of storage iron in patients appears to be a consequence of the defense strategy of macrophages during long-lasting inflammatory disorders. Decreased serum iron correlates to decreased haemoglobin concentrations. In view of this, the development of anaemia seems likely to result from the altered iron metabolism induced by stimulated macrophages. Low haemoglobin levels and associated hypoxia up-regulate the release of erythropoietin, which can explain why increased circulating erythropoietin is usually found in patients with anaemia.

Anemia↗
PubMed1991

Low haemoglobin in haemophilia children is associated with chronic immune activation.

Anaemia is a frequent complication in patients with human immunodeficiency virus type 1 (HIV-1) infection. We tested 14 children with severe haemophilia (9 HIV-1 antibody seropositive CDC stage IIA, 5 seronegative) for haemoglobin and urinary neopterin concentrations and found a negative correlation between neopterin and haemoglobin (rs = -0.745, p = 0.007; Spearman's rank correlation). This finding suggests that chronic immune activation, possibly along with the release of specific cytokines such as interferon gamma and tumor necrosis factor alpha may be involved in the pathogenesis of anaemia.

Adolescent↗
PubMed1991

Neopterin as a marker for activated cell-mediated immunity: application in malignant disease.

A review is presented on studies concerning neopterin determination in patients with malignant neoplastic diseases. Neopterin is produced chiefly by human macrophages through their activation by T-cell-derived interferon gamma. In vivo, determinationof neopterin in various body fluids provides a convenient way to monitor early events that are involved in cell-mediated immune responses. In malignant neoplasia, elevation of neopterin concentrations in body fluids depends on tumor type. Within a given type of tumor, more advanced stages are generally associated with higher levels than early disease. In a variety of different tumor types and sites, a significantly poorer prognosis was associated with high pretherapeutic neopterin concentrations. This predictive value is independent of several possible confounders such as stage or therapy. During follow-up malignant disease, neopterin elevations may predict deterioration of the clinical status of the patients and thereby provide a valuable additional marker for monitoring such patients. Possible immunobiological implications of the results are discussed.

Biomarkers, Tumor↗
PubMed1991

Postmortem evaluation of serum and urine neopterin concentrations.

Cellular immune response is accompanied by the release of neopterin. Increased neopterin levels in urine and serum are observed in patients during viral infections, autoimmune diseases, and allograft rejections and certain malignant diseases. We investigated postmortem neopterin concentrations in urine and serum samples taken from 32 corpses 3 to 69 h (mean 19.3 h) after death. Urine neopterin concentrations in corpses are similar to those of healthy live controls and are independent of the time after death. In contrast, serum neopterin concentrations are frequently greatly increased in corpses, and the levels are higher in sera collected more than 10 h after death in comparison with samples obtained earlier. Neopterin measurement in urine and serum samples of corpses is feasible. It appears likely that urine neopterin concentrations could aid the diagnosis of inflammatory diseases in corpses.

Adult↗
PubMed1991

Individual probability for onset of full-blown disease in patients infected with human immunodeficiency virus type 1.

Increased concentrations of neopterin, a marker for cell-mediated immune activation, and decreased numbers of CD4+ T cells, are predictors for progression of disease after infection with human immunodeficiency virus type 1. Previous studies have demonstrated different rates of onset of full-blown acquired immunodeficiency syndrome (AIDS) for groups of patients, defined by laboratory marker values, who were initially symptom-free. By re-analysis of one such study, we demonstrate how for an individual patient, the individual marker values, together with a prior risk estimate, can be converted into current or accumulated post-test probability of onset of AIDS at a certain time. We used a statistical technique suggested by Albert et al. (Clin Chem 1984;30:69-76), which allows incorporation of fixed and time-dependent covariates. Besides allowing individual projections, the method shows that the predictive abilities of CD4+ T cell numbers and of neopterin concentrations do not vary greatly with regard to time of observation; both laboratory markers independently modulate the underlying prior probability of AIDS onset, which is significantly increased with the passage of time.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Tetrahydrobiopterin-dependent formation of nitrite and nitrate in murine fibroblasts.

The present study demonstrates that murine dermal fibroblasts produce nitrite (NO2-) and nitrate (NO3-) upon treatment with interferon gamma (IFN-gamma). This formation is dependent on L-arginine and can be inhibited by the L-arginine analogue NG-monomethyl-L-arginine. The effect of IFN-gamma is drastically increased by cotreatment with tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), or lipopolysaccharide (LPS). The tested cytokines also induce formation of tetrahydrobiopterin in murine fibroblasts. Inhibition of guanosine triphosphate-cyclohydrolase I, the key enzyme of tetrahydrobiopterin de novo synthesis with 2,4-diamino-6-hydroxy-pyrimidine, leads to decreased formation of NO2- and NO3-. This effect can be reversed by addition of sepiapterin, which provides tetrahydrobiopterin via a salvage pathway. Methotrexate, which inhibits the salvage pathway, blocks the restoration of NO2- and NO3- production by sepiapterin. The cytotoxic effect of combinations of IFN-alpha with TNF-gamma, IL-1, or LPS is attenuated by inhibition of tetrahydrobiopterin synthesis. These results show that intracellular concentrations of tetrahydrobiopterin control the amount of NO2- and NO3- produced in situ and suggest that the role of cytokine-induced tetrahydrobiopterin synthesis is to provide cells with the active cofactor for production of nitrogen oxides.

Animals↗
PubMed1990

Neopterin formation and tryptophan degradation by a human myelomonocytic cell line (THP-1) upon cytokine treatment.

Determination of neopterin [D-erythro-6-(1',2',3'-trihydroxypropyl)pterin] in body fluids is a powerful diagnostic tool in a variety of diseases in which activation of cellular immune mechanisms is involved, such as certain malignancies, allograft rejection, and autoimmune and infectious diseases. In vitro, neopterin is released into the supernatant by peripheral blood-derived monocytes/macrophages upon stimulation with gamma-interferon. In parallel, cleavage of tryptophan by indoleamine 2,3-dioxygenase is induced. We report here that the human myelomonocytic cell line THP-1 forms neopterin and degrades tryptophan upon treatment with gamma-interferon. Like in macrophages alpha-interferon and beta-interferon induce these pathways only to a much smaller degree. The action of interferons is enhanced by cotreatment with tumor necrosis factor alpha, lipopolysaccharide, or dexamethasone. gamma-Interferon-induced neopterin formation and indoleamine 2,3-dioxygenase activity are increased by raising extracellular tryptophan concentrations. The pattern of intracellularly formed pteridines upon stimulation with gamma-interferon shows the unique characteristics of human monocytes/macrophages. Neopterin, monapterin, and biopterin are produced in a 50:2:1 ratio. Thus, the THP-1 cell line provides a permanent, easily accessible in vitro system for studying the induction and mechanism of neopterin formation.

Biopterins↗