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Biomedical subjects

D Fuchs

Publications and source records attributed to D Fuchs.

At least 127 records · Page 7Linked to original sources
PubMed1990

Production and characterization of a monoclonal antibody against neopterin.

We have produced and characterized the first monoclonal antibody against neopterin (D-erythro-6-(1,2,3,-trihydroxypropyl)pterin). The antibody specifically recognizes neopterin in a modified RIA. The binding capacity in this assay is 34%, the sensitivity limit of inhibition is 0.9 nmol/l. Cross-reactivity exists with monapterin (L-threo(1,2,3,trihydroxypropyl)pterin) in 30%, with other pteridines cross-reactivity has been found in less than 5%.

Animals↗
PubMed1990

Immune activation and decreased tryptophan in patients with HIV-1 infection.

We compared tryptophan, neopterin, and interferon-gamma (IFN-gamma) concentrations in serum and cerebrospinal fluid (CSF) of 22 patients with human immunodeficiency virus type 1 (HIV-1) infection. Tryptophan levels were found to be decreased in CSF and serum of patients whereas neopterin levels in CSF and serum and serum IFN-gamma concentrations were increased compared to healthy HIV-1 seronegatives. Tryptophan concentrations correlated negatively to neopterin concentrations, and serum neopterin concentrations correlated positively to IFN-gamma concentrations. Thus, decrease of tryptophan levels is associated with chronic immune stimulation in patients with HIV-1 infection. From the data it appears that reduced tryptophan in patients may result from induction of indoleamine (2,3)-dioxygenase by IFN-gamma.

Adult↗
PubMed1990

Urinary excretion of porphyrins is increased in patients with HIV-1 infection.

Urine concentrations of total porphyrins and of porphyrin precursors, delta-aminolaevulinic acid and porphobilinogen, were analysed in the first-morning urine samples of 36 people with established HIV-1 infection. For comparison, we also analysed the urine samples of 26 healthy HIV-seronegative people. In patients with HIV-1 infection concentrations of total porphyrins were found to be significantly higher than in healthy controls. Furthermore, there was a close correlation between concentrations of total porphyrins and porphobilinogen and urine neopterin concentrations in patients. Our data indicate an association between chronic immune activation and altered porphyrin metabolism. The data may provide a rationale for the observation of acute porphyria in patients with HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Increased serum neopterin in patients with HIV-1 infection is correlated with reduced in vitro interleukin-2 production.

Recently we have observed that the CD4+ T cell response of peripheral blood mononuclear cells (PBMC) to soluble antigens is the first to be lost in the course of HIV-1 infection followed by the loss of response to HLA alloantigens. In this study we compared serum neopterin concentrations of individuals with early stages of HIV-1 infection (stages WR1 and WR2, Walter Reed staging system) with in vitro interleukin-2 (IL-2) production of PBMC in response to stimulation with soluble antigens (influenza A virus and tetanus toxoid) and alloantigens. Neopterin concentrations were significantly higher in HIV-1-seropositive individuals who showed deficient IL-2 production in response to recall antigens only or to all of the stimuli tested in vitro, compared with HIV-1-seropositive individuals who exhibited no CD4+ T cell defects. No difference in serum neopterin concentrations was observed between the group that was functionally deficient to soluble antigens only versus those who were unresponsive to both types of stimuli. It appears that the selective loss of the MHC self-restricted CD4+ T cell function is associated with an increase in serum neopterin levels. Neopterin concentrations are an estimate of the activation status of macrophages. We conclude that defective in vitro production of lymphokines by T lymphocytes is associated with activated macrophages in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Correlation between neopterin, interferon-gamma and haemoglobin in patients with haematological disorders.

In this study, we further investigated a possible link between activation of cell-mediated immunity and anaemia in patients with haematological neoplasias. We compared serum concentrations of interferon-gamma and neopterin with haemoglobin levels. Significantly increased interferon-gamma and neopterin concentrations indicated persistent activation of cell-mediated immunity. Neopterin levels correlated significantly to interferon-gamma concentrations and inversely to haemoglobin levels. The data indicate an association between activated macrophages and the development of anaemia in patients with haematological neoplasias.

Adult↗
PubMed1990

Prereferral intervention: a prescriptive approach.

This investigation assessed effects of three increasingly inclusive versions of the Behavioral Consultation (BC) model on problem behavior of students in mainstream classrooms in an effort to develop an effective and efficient approach to prereferral intervention. Subjects were 43 general educators, their 43 most difficult-to-teach students (without disabilities), and 12 school consultants, representing seven inner-city middle schools. Teachers and students were assigned to three BC groups, representing least (BC 1), more (BC 2), and most (BC 3) inclusive variants of BC, and one control group. Preintervention, postintervention, and follow-up observations of student behavior indicated that more inclusive BC versions exerted stronger effects than the least inclusive variant in reducing problem behavior. Theoretical and practical implications for consultation-related activity are discussed.

Behavior Therapy↗
PubMed1990

Increased CSF neopterin levels in subarachnoid hemorrhage.

Neopterin concentrations, reflecting T-cell macrophage activation, were analyzed in serum and cerebrospinal fluid (CSF) obtained from 14 patients with subarachnoid hemorrhage (SAH). Neopterin concentrations were elevated in both the serum and CSF. The increase in neopterin concentrations was most marked in the CSF, rising from Days 1 to 3 through Days 6 to 9; levels were highest in patient suffering from delayed cerebral ischemia. The present data were interpreted as signs of an ongoing T cell activation both systemically and in the CSF compartment following SAH.

Adult↗
PubMed1990

Decreased serum tryptophan in patients with HIV-1 infection correlates with increased serum neopterin and with neurologic/psychiatric symptoms.

We investigated serum neopterin, tryptophan, and kynurenine concentrations in 23 HIV-1 seropositive patients (Walter Reed Stage 4-6). Ten patients presented with polyneuropathy and three with dementia, one of the patients with dementia also had polyneuropathy and dementia. We found significant associations between lower trytophan concentrations and neurologic/psychiatric symptoms. The negative correlation of tryptophan with kynurenine and neopterin concentrations indicates activity of indoleamine 2,3-dioxygenase (IDO) in patients. IDO can be induced by cytokines such as interferon-gamma and therefore low tryptophan levels may result from chronic immune stimulation in HIV-1 seropositives.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Parallel induction of tetrahydrobiopterin biosynthesis and indoleamine 2,3-dioxygenase activity in human cells and cell lines by interferon-gamma.

In all of eight tested human cells and cell lines with inducible indoleamine 2,3-dioxygenase (EC 1.13.11.17) tetrahydrobiopterin biosynthesis was activated by interferon-gamma. This was demonstrated by GTP cyclohydrolase I (EC 3.5.4.16) activities and intracellular neopterin and biopterin concentrations. Pteridine synthesis was influenced by extracellular tryptophan. In T 24-cell extracts, submillimolar concentrations of tetrahydrobiopterin stimulated the indoleamine 2,3-dioxygenase reaction.

Biopterins↗
PubMed1989

Characteristics of interferon induced tryptophan metabolism in human cells in vitro.

Interferon-gamma-induced tryptophan metabolism of human macrophages was compared to ten human neoplastic cell lines of various tissue origin and to normal dermal human fibroblasts. Tryptophan and metabolites were determined in supernatants of cultures, after incubation for 48 h, by high-performance liquid chromatography with ultraviolet and fluorescence detection. With the exception of two cell lines (Hep G 2, hepatoma and CaCo 2, colon adenocarcinoma) in all of the ten other cells and cell lines tryptophan degradation was induced by interferon-gamma. Five of these ten formed only kynurenine (SK-N-SH, neuroblastoma; T 24, J 82, bladder carcinoma; A 431, epidermoid carcinoma; normal dermal fibroblasts), three formed kynurenine and anthranilic acid (U 138 MG, glioblastoma; SK-HEP-1, hepatoma; A 549, lung carcinoma). Only one line, A 498 (kidney carcinoma) showed the same pattern of metabolites as macrophages (kynurenine, anthranilic acid and 3-hydroxyanthranilic acid). Interferon-gamma regulated only the activity of indoleamine 2,3-dioxygenase. All other enzyme activities detected were independent of interferon-gamma, as shown by the capacity of the cells to metabolize L-kynurenine or N-formyl-L-kynurenine. Increasing the extracellular L-tryptophan concentration resulted in a marked induction of tryptophan degradation by macrophages. Contrarily, a significant decrease of the tryptophan degrading activity was observed when the extracellular L-tryptophan concentration was increased 2-fold with SK-N-SH, T 24 and J 82, 4-fold with A 431 and A 549 and 10-fold with U 138 MG and SK-HEP-1. The activity was unaffected by extracellular L-tryptophan with dermal fibroblasts and A 498. Though interferon-gamma was the most potent inducer of tryptophan metabolism, interferon-alpha and/or -beta showed small but distinct action on some of the cells. In all cells which reacted to interferon-gamma by enhanced expression of class I and/or class II major histocompatibility complex antigens tryptophan degradation was also inducible. These results demonstrate that induction of indoleamine 2,3-dioxygenase is a common feature of interferon-gamma action, that the extent of this induction is influenced by extracellular L-tryptophan concentrations and that indoleamine 2,3-dioxygenase is the only enzyme in the formation of 3-hydroxyanthranilic acid from tryptophan which is regulated by interferon-gamma.

Cell Line↗
PubMed1989

AIDS incidence rates in Austria.

AIDS incidence rates were calculated for Austria based on cumulative data up to October 31st 1988. Geographical differences are obvious, provinces of the northwest showing higher incidence rates than south-east provinces. An association of high AIDS incidence rates with intravenous drug abuse is suggested by the data.

Acquired Immunodeficiency Syndrome↗