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C Murr

Publications and source records attributed to C Murr.

At least 37 records · Page 2Linked to original sources
PubMed1996

Streptococcal erythrogenic toxins induce neopterin formation in human peripheral blood mononuclear cells but not in the human myelomonocytoma cell line THP-1.

We tested whether the exposure of human monocytic cells to streptococcal erythrogenic toxins A, B, C and a streptococcal-derived Mitogert BX is associated with synthesis of neopterin in vitro. Neopterin production was not induced when the human myelomono-cytoma cell line THP-1 was stimulated with these toxins, and there was only a slight co-stimulatory effect of streptococcal erythrogenic toxin A together with interferon-gamma stimulation. However, these toxins induced interferon-gamma and further neopterin production in peripheral blood mononuclear cells of three healthy individuals. This neopterin formation could be blocked by anti-human interferon-gamma. From our investigations we conclude that there is no direct effect of streptococcal erythrogenic toxins on neopterin production by monocytic cells. However, the data obtained in peripheral blood mononuclear cell culture imply that these toxins are able to stimulate neopterin production in humans via the induction of huge amounts of interferon-gamma.

Biopterins↗
PubMed1995

Urinary neopterin excretion in patients with squamous carcinoma of the oral cavity.

Urinary neopterin concentrations were studied in 30 patients with squamous carcinoma or adenoid cystic carcinoma of the oral cavity. Compared to healthy controls 19 patients (63%) had increased neopterin concentrations. There was a statistically significant correlation between neopterin levels and tumor differentiation but no correlation of neopterin values with tumor size. Longitudinal studies will be necessary to evaluate a potential usefulness of neopterin concentrations to predict prognosis in squamous carcinomas of the oral cavity.

Adult↗
PubMed1995

Conformational investigation of the cofactor (6R,1'R,2'S-)-5,6,7,8-tetrahydrobiopterin.

(6R,1'R,2'S)-5,6,7,8-Tetrahydrobiopterin is an essential cofactor for several enzymes. Different theoretical models (molecular mechanics, semiempirical quantum chemical calculations) investigating its stereostructure have yielded diverging answers. To clarify these issues, combined molecular mechanical and ab initio quantum chemical calculations were performed, investigating both the axial and the equatorial orientation of the dihydroxypropyl side-chain. After geometry optimization, the resulting most stable structures were subjected to systematic variation of two side-chain torsional angles in order to study the conformational flexibility. The axial side-chain orientation is slightly more stable than the equatorial form. Two weak intramolecular hydrogen bonds contribute to stabilization of the axial conformer, while in the equatorial conformer only one hydrogen bond is detected. An 8 ps molecular dynamical simulation at 310 K suggests that, at realistic temperatures, the molecule is flexible enough to undergo internal motions (rotations, vibrations), rendering questionable the biological significance of mere conformational properties.

Biopterins↗
PubMed1995

Effect of neopterin and 7,8-dihydroneopterin on tumor necrosis factor-alpha induced programmed cell death.

Tumor necrosis factor-alpha and the formation of reactive oxygen intermediates are central mediators of apoptosis. Recent data indicated a role of neopterin and 7,8-dihydroneopterin in oxygen radical mediated processes. We have therefore investigated the effect of neopterin-derivatives on TNF alpha induced apoptosis of the monocyte-like cell line U937. At an elevated concentration 7,8-dihydroneopterin was found to superinduce TNF alpha mediated programmed cell death due to the formation of reactive oxygen intermediates. Our results imply that in combination with TNF alpha high concentrations of 7,8-dihydroneopterin enhances apoptosis due to oxidative stress on cells.

Acetylcysteine↗
PubMed1995

Neopterin and soluble tumor necrosis factor receptor type I in alcohol-induced cirrhosis.

Alcohol-induced cirrhosis (AC) is accompanied by disturbances of immune function and cytokine production. To better define the pattern of cytokine synthesis in this disease and to relate it to the immune activation state, we measured circulating levels of soluble tumor necrosis factor receptor p55 (sTNFR-55) and neopterin in a group of 85 patients with AC (classified according to the Child-Pugh score of severity of liver disease) and 43 healthy volunteers. Serum concentrations of sTNFR-55 and neopterin were significantly raised in patients with AC. Moreover, concentrations of sTNFR-55 were significantly higher in patients with more severe disease compared with the group with lower severity. There were significant correlations between sTNFR-55 and neopterin levels in patients and controls. The results contribute to affirm the existence of an immune activation state in AC that could be responsible for the development of the disease and clinical complications.

Biopterins↗
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

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↗
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

HIV myelopathy.

Explore the source record for details and available documents.

Biopterins↗
PubMed1994

Neopterin production and tryptophan degradation in acute Lyme neuroborreliosis versus late Lyme encephalopathy.

Fourteen patients with Borrelia burgdorferi infection were investigated for possible abnormalities of tryptophan and neopterin metabolism. Four patients (2 were investigated before therapy, 2 when therapy had been already started) had acute Lyme neuroborreliosis, and 10 patients were investigated months to years after an acute infection. Increased concentrations of neopterin and of the tryptophan-degradation product, L-kynurenine, were detected in the cerebrospinal fluid of patients with acute Lyme neuroborreliosis; one patient presented with subnormal tryptophan. Similar but less marked changes were seen in the treated patients and in some of the patients with Lyme encephalopathy. No such abnormalities were seen in the serum of the patients. The data indicate a role of the immune system and particularly of endogenously formed cytokines, like interferon-gamma and tumour necrosis factor-alpha, effecting tryptophan and neopterin metabolism in patients with acute Lyme neuroborreliosis.

Acute Disease↗
PubMed1994

Neopterin--its clinical use in urinalysis.

Increased amounts of neopterin are released during cellular immune response. Neopterin concentrations can be monitored in serum and urine of patients since neopterin is removed from the circulation by renal excretion. In allograft recipients, rising neopterin concentrations indicate rejection episodes early. Neopterin concentrations correlate with the extent and activity of viral infections, malignancies, and autoimmune diseases. We investigated excretion kinetics of neopterin in a rhesus monkey which received a high dose of neopterin intravenously. A sharp increase of urinary neopterin concentrations was observed, and from the data the half-life of neopterin in the circulation was estimated to be 90 minutes. By comparing urine and serum neopterin concentrations in HIV seropositive and seronegative human individuals, a strong correlation and similar diagnostic sensitivity between urine and serum values was observed. Thus, neopterin concentrations in serum or urine seem of equal value for diagnostic application as long as renal function is normal.

Animals↗
PubMed1993

Maple syrup urine disease: metabolic decompensation monitored by proton magnetic resonance imaging and spectroscopy.

Metabolic decompensation of maple syrup urine disease in a 3.5-year-old boy was monitored by means of proton magnetic resonance imaging and spectroscopy. In the acute stage, imaging showed diffuse cerebral edema. Proton spectra showed an elevation of lactate and a previously unassigned resonance at 1 ppm. This peak disappeared with normalization of branched-chain amino acids and oxoacids in the plasma and cerebrospinal fluid. In vitro spectroscopy of these metabolites at 1.5 T confirmed the chemical shift position of their methyl resonances at 1 ppm. The duration of lactate elevation correlated with the presence of brain edema and coma. These results demonstrate that magnetic resonance imaging can monitor therapeutic effects, and suggest that proton spectroscopy can detect cerebral accumulation of branched-chain amino acids and oxoacids in maple syrup urine disease.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗