PubMed Health⌕ Search

Biomedical subjects

D Fuchs

Publications and source records attributed to D Fuchs.

At least 397 records · Page 22Linked to original sources
PubMed1990

Comparison of serum and urine neopterin concentrations in patients with HIV-1 infection.

Urine and serum neopterin concentrations are now widely used to monitor patients with HIV-1 infection. However, there are no published studies comparing the levels in urine and serum, and relating both to the patients' immune status. Urine and serum neopterin concentrations correlated closely in our study population of 37 HIV-1 seropositive patients (34 homosexuals, 3 drug addicts) and 10 HIV-1 seronegative homosexuals. Our data further show that urine and serum neopterin concentrations correlate almost identically with the clinical and immunological presentation of HIV-1 infected individuals, as expressed by the Walter Reed Staging classification. In addition, there was no difference between the correlation of neopterin concentrations in either serum or urine with the Quetelet indices. It will depend on the clinical situation whether blood or urine sampling is preferred. Collection and handling of urine samples from HIV infected patients is less risky to health care personnel in HIV settings.

Adult↗
PubMed1990

Tetrahydrobiopterin biosynthetic activities in human macrophages, fibroblasts, THP-1, and T 24 cells. GTP-cyclohydrolase I is stimulated by interferon-gamma, and 6-pyruvoyl tetrahydropterin synthase and sepiapterin reductase are constitutively present.

Interferon-gamma induces tetrahydrobiopterin biosynthesis in human cells and cell lines. Macrophages are peculiar in the formation of large amounts of neopterin derivatives as compared to tetrahydrobiopterin (Werner, E. R., Werner-Felmayer, G., Fuchs, D., Hausen, A., Reibnegger, G., and Wachter, H. (1989) Biochem J. 262, 861-866). Here we compare the impact of interferon-gamma treatment on activities of GTP-cyclohydrolase I (EC 3.5.4.16), 6-pyruvoyl tetrahydropterin synthase, and sepiapterin reductase (EC 1.1.1.153) in human peripheral blood-derived macrophages, normal dermal fibroblasts, THP-1 myelomonocytic cells, and the T 24 bladder transitional-cell carcinoma line. Upon interferon-gamma treatment, GTP-cyclohydrolase I activity is increased 7- to 40-fold, whereas 6-pyruvoyl tetrahydropterin synthase and sepiapterin reductase activities, which are constitutively present in all four investigated cells, remain unchanged. In fibroblasts and T 24 cells GTP cyclohydrolase I activity is the rate-limiting step of tetrahydrobiopterin biosynthesis. In macrophages and in THP-1 cells, however, the induced GTP cyclohydrolase I activity is higher than the 6-pyruvoyl tetrahydropterin synthase activity, leading to the accumulation of neopterin and neopterin phosphates.

Alcohol Oxidoreductases↗
PubMed1990

Value of urinary neopterin in the differential diagnosis of bacterial and viral infections.

Neopterin is released by stimulated macrophages. In this study we analyzed the diagnostic potential of urinary neopterin concentrations in patients with bacterial and viral infection. All but one of 17 patients with viral infection had increased urinary neopterin concentrations. Patients with bacterial urinary tract infection also showed increased neopterin concentrations, whereas patients with bacterial pneumonia had significantly lower neopterin levels. In addition, patients with acute bacterial pneumonia had lower neopterin levels than patients with protracted infection. A significant inverse correlation between urinary neopterin and hemoglobin concentrations was found. Neopterin concentrations could serve as a helpful additional marker of infectious diseases. Combined with other clinical and laboratory parameters it is a useful parameter for distinguishing between viral and bacterial origins of infection, as was shown by multivariate stepwise linear discriminant analysis.

Adult↗
PubMed1990

Urinary neopterin concentrations and T-cell subset data in HIV-1 infection.

We investigated the ability of urinary neopterin concentrations and T-cell subset data, and their ratios to discriminate between anti-HIV-1 seronegatives, seropositives, and AIDS cases. Using receiver-operated-characteristics curves, neopterin levels were shown to provide the best discrimination. Of the ratios derived from the single variables, neopterin per CD4+ cell counts and neopterin per CD4+/CD8+ cell ratio were superior to the CD4+/CD8+ cell ratio. Multivariate analyses were performed using a generalized likelihood ratio approach as well as linear discriminant analysis. The combination of neopterin concentration and CD4+ T-cell count is well suited to discriminate between various stages of HIV-1 infection and, therefore, we recommend using more than one assay to evaluate disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Age dependency of the progression of HIV disease in haemophiliacs; predictive value of T cell subset and neopterin measurements.

Sixteen HIV-seropositive haemophiliacs were followed up for 42 months and 9 other patients for 24 months. All patients were infected in 1983 or 1984. T cell subsets and serum neopterin levels were measured twice a year. The patients were divided into three groups according to their age in 1989: group A (children) less than 14 years old (n = 6); group B (adolescents) 14-20 years old (n = 8); group C (adults) greater than 20 years old (n = 11). At the last measurement performed in November, 1989, patients of group A had significantly higher absolute number and percentage of CD4+ lymphocytes and significantly lower serum neopterin levels than patients of group B and C. In addition, the percentage of the activated, CD3+ DR+ lymphocytes was also significantly higher in the adult-adolescent group than in the children group. Until the end of December, 1989, AIDS developed in 0, 1 and 2 patients and ARC was diagnosed in 0, 5, and 2 patients of groups A, B, and C, respectively. The progression of the HIV disease towards AIDS in these patients was predicted by the T cell subset and neopterin measurements performed in 1987. Only those 3 patients who progressed to AIDS had CD4+ cells less than 350/microliters and a neopterin value of more than 20 nmol/l. These findings confirm previous observations indicating that in patients with haemophilia the progression of HIV disease is influenced by age: a relatively slow progression can be expected in prepuberty children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Immune activation markers to predict AIDS and survival in HIV-1 seropositives.

Neopterin concentrations in body fluids of HIV-1 seropositives provide predictive information. In 1986, we examined serum and urine neopterin concentrations in 29 HIV-1 seropositives. Serum levels of soluble IL-2 receptor (sIL2R), soluble CD8 (sCD8), tumour necrosis factor alpha (TNF-alpha) and circulating immune complexes (CIC) were retrospectively analysed in 1989. All individuals had increased serum and urine neopterin, sIL2R and CIC concentrations, 27/29 had increased sCD8 concentrations, whereas all had normal TNF-alpha levels. During a 3-year follow-up, high urine and serum neopterin concentrations were significantly associated with progression to AIDS and with the occurrence of AIDS-associated death. Both neopterin variables were of similar predictive value (p less than 0.001, generalized Wilcoxon test). sIL2R concentrations were of borderline significance in predicting the onset of AIDS (p = 0.05). All other parameters lacked predictive information in our study. We conclude, that chronic immune activation is detectable in almost all HIV-1 seropositives. Chronic immune activation may be associated with HIV-1 replication and may contribute to the immunopathology of HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
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↗