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D Fuchs

Publications and source records attributed to D Fuchs.

At least 271 records · Page 15Linked to original sources
PubMed1994

Increased serum concentrations of soluble tumor necrosis factor receptors in HIV-infected individuals are associated with immune activation.

Serum concentrations of soluble tumor necrosis factor receptors (sTNF-Rs) were measured in 61 human immunodeficiency virus (HIV)-infected individuals. Thirty-five percent of these had increased serum concentrations of sTNF-R type I (p55) (sTNF-R55) and 82% had increased concentrations of sTNF-R type II (p75) (sTNF-R75). The extent of the increase of sTNF-R75 was greater in more advanced HIV infection (p = 0.046) as it was measured by dividing the 61 individuals into two groups according to the median of the CD4+ T-cell count. However, the increase in concentrations of sTNF-R55 in the group with a CD4+ T-cell count below the median was only moderate and did not reach statistical significance. A strong correlation was found between sTNF-R75 and the soluble immune activation markers beta 2-microglobulin (rs = 0.74, p < 0.0001) and urinary neopterin (rs = 0.67, p < 0.0001), and a less strong correlation was found with interferon-gamma (rs = 0.51, p = 0.0001). The correlations observed for sTNF-R55 were also significant but were always weaker than that of sTNF-R75. A weak inverse correlation was found between the number of CD4+ T cells and sTNF-R75 (rs = -0.33, p = 0.012), but no such correlation was observed with sTNF-R55. Our findings suggest that increased concentrations of serum sTNF-Rs in HIV infection are linked to immune activation, in which synergistic actions of interferon-gamma and the TNF-alpha system are likely to play an important role.

Adolescent↗
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↗
PubMed1993

Neopterin modulates toxicity mediated by reactive oxygen and chloride species.

Neopterin, a pyrazino-pyrimidine derivative, is synthesized in excess by human monocytes/macrophages upon stimulation with interferon-gamma, a cytokine derived from activated I cells. Neopterin is furthermore produced constitutively. A relatively constant ratio between neopterin and its reduced form. 7,8-dihydroneopterin, has been described in human serum. In the study presented here we tested the ability of neopterin and its reduced form to modulate the effects of cytotoxic substances like hydrogen peroxide or hypochlorous acid and N-chloramine derivatives. We show that 7,8-dihydroneopterin potently reduces biological and chemical effects of these substances independently from the pH value. In contrast, at slightly alkaline pH (pH 7.5) neopterin enhances hydrogen peroxide and chloramine-T activity. This is demonstrated by increase of signal intensity in a luminol assay and also by enhancement of toxicity towards bacteria. Thus, the macrophage derived substance neopterin is able both to enhance and to reduce cytotoxicity in dependence of pH value and its oxidation state, and it may have a pivotal role in modulation of macrophage mediated effector mechanism.

Animals↗
PubMed1993

Effect of pteridine derivatives on intracellular calcium concentration in human monocytic cells.

Pteridines are heterocyclic compounds which are synthesized and released by human monocytes/macrophages following stimulation by interferon-gamma. Their concentration in various body fluids proved to be indicative for the stimulation of the cellular immune system, and determination of pteridines has become an important diagnostic tool. We show that pteridine derivatives, namely neopterin (N), 7,8-dihydroneopterin (NH2), and 5,6,7,8-tetrahydrobiopterin (BH4) increase intracellular calcium (Cai) in human monocytic cells. Significant increases of Cai are observed at 10 nmol/l NH2, at 100 nmol/l BH4 and at 1 mol/l N, i.e. at concentrations encountered in vivo. At a concentration of 1 mumol/l, Cai is increased (from a control value of 145 +/- 7 nmol/l) to 464 +/- 62 nmol/l (NH2), 340 +/- 41 nmol/l (BH4) and 344 +/- 46 nmol/l (N), respectively. The increase of Cai depends on the presence of extracellular calcium and is likely to be due to activation of a calcium channel. We show that the absence of extracellular calcium or the addition of lanthanum ions to the extracellular fluid fully reverses the pteridine-induced increase of Cai. According to these observations, pteridines may mimic the effects of other inflammatory mediators on monocytic cells and seem to be involved in the crosstalk of immunocompetent cells.

Biopterins↗
PubMed1993

Pteridine biosynthesis in human endothelial cells. Impact on nitric oxide-mediated formation of cyclic GMP.

Stimulation of nitric oxide (NO) synthase in endothelial cells by Ca2+ influx leads to increased intracellular levels of cGMP. NO synthase from various sources is known to use tetrahydrobiopterin, flavins, and NADPH as cofactors. We studied the effect of interferon-gamma, tumor necrosis factor-alpha, and lipopolysaccharide on tetrahydrobiopterin biosynthetic activities in human umbilical vein endothelial cells (HUVEC). These stimuli led to an up to 40-fold increase of GTP cyclohydrolase I (EC 3.5.4.16) activity and to increased accumulation of neopterin and tetrahydrobiopterin in HUVEC. Further enzyme activities of tetrahydrobiopterin biosynthesis, i.e. 6-pyruvoyl tetrahydropterin synthase and sepiapterin reductase (EC 1.1.1.153), remained unchanged. NO synthase activity in protein fractions from homogenates of cells treated with interferon-gamma plus tumor necrosis factor-alpha was not influenced as compared with untreated controls. However, interferon-gamma alone or in combination with tumor necrosis factor-alpha significantly increased intracellular cGMP formation in intact HUVEC by 50 and 80%, respectively. These stimuli increased intracellular tetrahydrobiopterin concentrations up to 14-fold. NO-triggered cGMP formation was similarly increased by incubation of otherwise untreated cells with sepiapterin, leading to elevated intracellular tetrahydrobiopterin levels. Thus, cytokines indirectly stimulate the activity of constitutive NO synthase in HUVEC by upregulating production of the cofactor tetrahydrobiopterin.

Amino Acid Oxidoreductases↗
PubMed1993

Ca2+/calmodulin-dependent nitric oxide synthase activity in the human cervix carcinoma cell line ME-180.

We show here that the human cervix carcinoma cell line ME-180 expresses a constitutive nitric oxide (NO) synthase, as demonstrated by formation of [3H]citrulline and nitrite. The enzyme is dependent on tetrahydrobiopterin, NADPH, flavins and Ca2+/calmodulin. Enzyme activity is located in the cytosol rather than in the membrane fraction and can be inhibited by NG-monomethyl-L-arginine (NMMA). An antiserum to NO synthase purified from porcine cerebellum inhibited the enzyme activity. ME-180 cells released NO, as was shown by stimulation of guanylate cyclase (EC 4.6.1.2) in RFL-6 detector cells; this release was stimulated 8-fold by the Ca2+ ionophore A23187 and 2-fold by increasing the intracellular tetrahydrobiopterin levels with cytokines. This is the first characterization of a Ca2+/calmodulin-dependent NO synthase activity in human epithelial-type tumour cells.

Amino Acid Oxidoreductases↗